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Okoli GN, Grossman Moon A, Soos AE, Neilson CJ, Harper DM. Hepatitis B vaccination initiation and vaccination series completion: An in-depth systematic evidence review, with meta-analysis of associations with individual socioeconomic and health-related factors. Vaccine 2025; 55:127051. [PMID: 40154242 DOI: 10.1016/j.vaccine.2025.127051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 03/14/2025] [Accepted: 03/17/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Associations between hepatitis B vaccination and individual socioeconomic/health-related factors have not been summarised. METHODS We conducted a systematic review with meta-analysis (PROSPERO: CRD42023445721) wherein we grouped study populations into a paediatric population (<18-year-olds), community-dwelling adults (≥18-year-olds of average risk), persons at a higher risk of exposure, and persons with a chronic condition(s). We pooled appropriate multivariable-adjusted results using an inverse variance random-effects model, with the pooled results expressed as odds ratios and associated 95% confidence intervals. RESULTS We included 83 cross-sectional studies. Thirty-nine studies reported on vaccination initiation, and 51 reported on vaccination series completion. In the paediatric population, being a child of an Asian versus White mother increased the odds of vaccination initiation, whereas a low versus high mother's socioeconomic status and birth in a health facility versus home birth increased the odds of vaccination series completion. In community-dwelling adults, there were increased odds of vaccination initiation with being younger, a White versus Black/Hispanic person, a health professional, higher education, HIV/hepatitis B screening, influenza vaccination in the past year, health insurance, and health care utilisation. There were increased odds of vaccination series completion with factors like initiation. In persons at a higher risk of exposure, older age, higher education, HIV/hepatitis B screening, influenza vaccination in the past year, being married/cohabiting, and training on infection increased the odds of vaccination initiation. In contrast, drug use, HIV/hepatitis B screening, being married/cohabiting, being female, being a current/former smoker, and having more health worker experience increased the odds of vaccination series completion. In persons with chronic condition(s), younger age was associated with increased odds of vaccination initiation, whereas higher education and being a health professional increased the odds of vaccination series completion. CONCLUSIONS Several individual socioeconomic and health-related factors may influence hepatitis B vaccination, particularly in community-dwelling adults and persons at higher risk of exposure. Our findings may inform targeted messaging to optimise hepatitis B vaccination.
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Affiliation(s)
- George N Okoli
- Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
| | | | - Alexandra E Soos
- University of Michigan Medical School, University of Michigan, Michigan, USA
| | - Christine J Neilson
- Neil John Maclean Health Sciences Library, University of Manitoba, Winnipeg, MB, Canada
| | - Diane M Harper
- Departments of Family Medicine and Obstetrics & Gynecology, University of Michigan, Michigan, USA
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Cancemi G, Campo C, Caserta S, Rizzotti I, Mannina D. Single-Agent and Associated Therapies with Monoclonal Antibodies: What About Follicular Lymphoma? Cancers (Basel) 2025; 17:1602. [PMID: 40427101 PMCID: PMC12109769 DOI: 10.3390/cancers17101602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 05/01/2025] [Accepted: 05/07/2025] [Indexed: 05/29/2025] Open
Abstract
Monoclonal antibodies (mAbs) have become a cornerstone in the treatment of follicular lymphoma (FL), offering highly specific therapeutic targeting that enhances efficacy while minimizing systemic toxicity. Their mechanisms of action include antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and direct apoptotic signaling, effectively mediating malignant B-cell depletion. Anti-CD20 mAbs, such as rituximab and obinutuzumab, have significantly improved progression-free survival (PFS) and overall survival (OS), establishing immunochemotherapy as the standard of care for FL. However, the emergence of treatment resistance, often characterized by CD20 antigen downregulation or immune escape, has prompted the development of next-generation mAbs with enhanced effector functions. Bispecific antibodies (BsAbs), which simultaneously engage CD20-expressing tumor cells and CD3-positive cytotoxic T cells, have emerged as a novel immunotherapeutic strategy, redirecting T-cell activity to eliminate malignant B cells independently of major histocompatibility complex (MHC) antigen presentation. Additionally, antibody-drug conjugates (ADCs) offer a targeted cytotoxic approach by delivering potent chemotherapeutic payloads directly to tumor cells while limiting off-target effects. The integration of mAbs with immune checkpoint inhibitors and immunomodulatory agents is further enhancing treatment outcomes by overcoming immunosuppressive mechanisms within the tumor microenvironment. Despite these advancements, challenges remain, including optimizing the treatment sequence, mitigating immune-related toxicities-particularly cytokine release syndrome (CRS)-and identifying predictive biomarkers to guide patient selection. As the role of monoclonal antibodies continues to expand, their integration into therapeutic regimens is transforming the management of FL, paving the way for chemotherapy-free treatment approaches and long-term disease control. This review provides an updated overview of mAbs therapies for FL, emphasizing the advances brought by BsAbs and ADCs toward more tailored and effective treatments.
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Affiliation(s)
- Gabriella Cancemi
- Hematology Unit, Oncology-Hematology Department, Azienda Ospedaliera Papardo, 98158 Messina, Italy; (G.C.); (C.C.); (I.R.)
| | - Chiara Campo
- Hematology Unit, Oncology-Hematology Department, Azienda Ospedaliera Papardo, 98158 Messina, Italy; (G.C.); (C.C.); (I.R.)
| | - Santino Caserta
- Hematology Unit, Department of Human Pathology in Adulthood and Childhood “Gaetano Barresi”, University of Messina, Via Consolare Valeria, 98125 Messina, Italy;
| | - Iolanda Rizzotti
- Hematology Unit, Oncology-Hematology Department, Azienda Ospedaliera Papardo, 98158 Messina, Italy; (G.C.); (C.C.); (I.R.)
| | - Donato Mannina
- Hematology Unit, Oncology-Hematology Department, Azienda Ospedaliera Papardo, 98158 Messina, Italy; (G.C.); (C.C.); (I.R.)
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Kankılıç AT, Karakoyun Ö, Ayhan E. Risk of HBV reactivation in psoriasis vulgaris patients receiving biological agent therapy. Cutan Ocul Toxicol 2025; 44:113-117. [PMID: 40056433 DOI: 10.1080/15569527.2025.2475444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 02/11/2025] [Accepted: 02/26/2025] [Indexed: 03/10/2025]
Abstract
OBJECTIVE Recently, adalimumab has become an important drug frequently used by dermatologists in the treatment of Hidradenitis suppurativa. While there are many publications by rheumatologists about the risk of hepatitis B and tuberculosis reactivation, the literature on reactivation in the treatment of hidradenitis is not extensive. With this study, we wanted to emphasize that adalimumab is a safe drug despite the risk of hepatitis B and tuberculosis reactivation and the importance of porphylaxis during the treatment of hidradenitis suppurativa. METHODS In this study, data from 462 HS patients followed up at the Dicle University Dermatology Clinic between 1 January 2017 and 30 June 2024 were retrospectively analyzed. Adalimumab use was detected in 56 of the 462 patients. Patients over 18 years of age and used adalimumab for at least 6 months were selected for this study. Two of these patients were not included in the study because they did not meet the criteria for age and duration of adalimumab use. RESULTS Of the 12 patients at risk of hepatitis B reactivation during adalimumab treatment, 8 received entecavir, and 4 received tenofovir prophylaxis. No hepatitis B reactivation was observed in any of the 12 patients during adalimumab treatment. Among the 54 patients, 4 were at risk of TB reactivation, and 4 received isoniazid as preophylactic treatment. None of the 4 patients were observed to have TB reactivation. CONCLUSION Adalimumab has become a frequently preferred drug in the treatment of hidradenitis, and it is known that there is a risk of hepatitis b and TBc reactivation, which should be prevented. Despite these risks, we found that adalimumab can be safely used to treat hidradenitis suppurativa, especially with the use of prophylaxis.
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Affiliation(s)
- Ayşegül Tel Kankılıç
- Department of Dermatology, Dicle University Faculty of Medicine, Diyarbakır, Turkey
| | - Ömer Karakoyun
- Department of Dermatology, Dicle University Faculty of Medicine, Diyarbakır, Turkey
| | - Erhan Ayhan
- Department of Dermatology, Dicle University Faculty of Medicine, Diyarbakır, Turkey
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Ozturk Cerik H, Aldemir O. Spontaneous reactivation of resolved HBV infection in the absence of immunosuppression: case report and literature review. Diagn Microbiol Infect Dis 2025; 111:116675. [PMID: 39754919 DOI: 10.1016/j.diagmicrobio.2024.116675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Revised: 12/28/2024] [Accepted: 12/28/2024] [Indexed: 01/06/2025]
Abstract
It is estimated that two billion people worldwide are infected with hepatitis B. In such cases, patients exposed to the virus may experience HBV-reactivation(HBVr), which is usually due to immunosuppression. It is not anticipated that spontaneous-HBVr will occur in the absence of immunosuppression in resolved HBV. In the literature, only 3 cases with spontaneous-HBVr have been reported in this setting. Our case is an 81-year-old female patient who was hospitalized for intracranial hemorrhage and spontaneous-HBVr was detected on the 24th day of hospitalization. Initially, HBsAg:(-) and anti-HBs were 77.5IU/L. Subsequent follow-up, liver function tests were increased, HBsAg:(+), anti-HBs:(-), and HBV-DNA:2513IU/ml were detected. The patient had several comorbidities such as diabetes-mellitus, hypertension, and chronic-obstructive-pulmonary-disease, but no history of immunosuppressive treatment. Following the diagnosis of spontaneous-HBVr, entecavir was initiated, resulting in the achievement of HBV-DNA negativity. It should be kept in mind that comorbidities like aging, surgery, or diabetes may trigger spontaneous-HBVr.
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Affiliation(s)
- Hatun Ozturk Cerik
- Ordu University School of Medicine, Assistant Professor Doctor Department of Infectious Disease and Clinical Microbiology Bucak neighbourhood, Nefsi Bucak street No:94/1, 52200 Altinordu, Ordu, Türkiye.
| | - Ozlem Aldemir
- Ministry of Health Sivas Numune Hospital, Specialist Doctor Department of Infectious Diseases and Clinical Microbiology, Yesilyurt neighbourhood, Sifa street No:4, 58060 Sivas, Türkiye.
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Androutsakos T, Dimitriadis K, Koutsompina ML, Vassilakis KD, Pouliakis A, Fragoulis GE. Hepatitis B reactivation in PsA patients: an SLR and meta-analysis for IL-17, IL-23 and JAK inhibitors. Rheumatology (Oxford) 2025; 64:935-942. [PMID: 39153010 DOI: 10.1093/rheumatology/keae445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 07/16/2024] [Accepted: 07/29/2024] [Indexed: 08/19/2024] Open
Abstract
OBJECTIVES HBV reactivation (HBVr) constitutes a side effect of the treatment of autoimmune rheumatic diseases. Even though HBVr risk of conventional synthetic DMARDs (csDMARDs) and anti-tumor necrosis factor (anti-TNF) agents has long been established, the risk of targeted synthetic (ts)DMARDs and anti-interleukin (anti-IL) agents remains largely unknown. METHODS We conducted a SLR (PubMed, Scopus and EMBASE) and meta-analysis to examine the HBVr risk for the following: anti-IL17, anti-IL12/23, anti-IL23 and JAK-inhibitors in patients with chronic HBV infection (HBsAg presence or detectable HBV-DNA) and in patients with prior HBV infection (HBcAb-positive and HBsAg-negative). Meta-analysis was performed using both the fixed and random effects method and was conducted using the R computing language. RESULTS Overall, our study revealed a low HBVr risk of <6% in all agents; the risk was significantly higher for people having chronic compared with those with resolved HBV (14.4% vs 5.1%, respectively P < 0.01). There was no difference among different drugs in the HBVr rates [anti-IL-17: 4% (95% CI: 1-9%), anti-IL-12/IL-23: 2% (95% CI: 0-5%), JAK-inhibitors: 4% (95% CI: 1-8%), anti-IL23: 0%]. Of note, HBVr rate reached 28% in patients with chronic HBV who did not receive anti-viral treatment. For patients with resolved hepatitis, the respective percentage was 4.7%. CONCLUSION Overall, our meta-analysis shows that patients with chronic HBV receiving anti-IL-17, anti-IL-12/23, anti-IL-23 and JAK-inhibitors have significant risk for HBVr, especially if they are not under anti-viral treatment. In contrast, resolved HBV seems to offer minor risk for HBVr even without anti-viral treatment.
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Affiliation(s)
- Theodoros Androutsakos
- Department of Pathophysiology, National and Kapodistrian University of Athens, Athens, Greece
| | - Konstantinos Dimitriadis
- Department of Clinical Therapeutics, 'Alexandra' hospital, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Konstantinos D Vassilakis
- First Department of Internal Medicine, Propaedeutic Clinic, "Laiko" Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Avraam Pouliakis
- Second Department of Pathology, National and Kapodistrian University of Athens, Athens, Greece
| | - George E Fragoulis
- First Department of Internal Medicine, Propaedeutic Clinic, "Laiko" Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Adewuyi O‘S, Balogun MS, Otomaru H, Abimiku A, Ahumibe AA, Ilori E, Luong QA, Mba N, Avong JC, Olaide J, Okunromade O, Ahmad A, Akinpelu A, Ochu CL, Olajumoke B, Abe H, Ihekweazu C, Ifedayo A, Toizumi M, Moriuchi H, Yanagihara K, Idris J, Yoshida LM. Molecular Epidemiology, Drug-Resistant Variants, and Therapeutic Implications of Hepatitis B Virus and Hepatitis D Virus Prevalence in Nigeria: A National Study. Pathogens 2025; 14:101. [PMID: 39861062 PMCID: PMC11768191 DOI: 10.3390/pathogens14010101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 01/12/2025] [Accepted: 01/13/2025] [Indexed: 01/27/2025] Open
Abstract
Information on circulating HBV (sub-)genotype, variants, and hepatitis D virus (HDV) coinfection, which vary by geographical area, is crucial for the efficient control and management of HBV. We investigated the genomic characteristics of HBV (with a prevalence of 8.1%) and the prevalence of HDV in Nigeria. We utilised 777 HBV-positive samples and epidemiological data from the two-stage sampled population-based, nationally representative Nigeria HIV/AIDS Indicator and Impact Survey conducted in 2018. We assessed 732 HBV DNA-extracted samples with detectable viral loads (VLs) for (sub-)genotypes and variants by whole-genome pre-amplification, nested PCR of the s-and pol-gene, and BigDye Terminator sequencing. We conducted HDV serology. In total, 19 out of the 36 + 1 states in Nigeria had a high prevalence of HBV (≥8%), with the highest prevalence (10.4%) in the north-central geopolitical zone. Up to 33.2% (95% CI 30.0-36.6) of the participants had detectable VLs of ≥300 copies/mL. The predominant circulating HBV genotype was E with 98.4% (95% CI 97.1-99.1), followed by A with 1.6% (95% CI 0.9-2.9). Drug-resistant associated variants and immune escape variants were detected in 9.3% and 0.4%, respectively. The seroprevalence of HDV was 7.34% (95% CI 5.5-9.2). Nigeria has subtype E as the major genotype with many variants.
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Affiliation(s)
- Oludare ‘Sunbo Adewuyi
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan (H.M.)
- Department of Paediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan (M.T.)
- Nigeria Centre for Disease Control and Prevention, Abuja 240102, Nigeria (O.O.); (C.L.O.)
| | - Muhammad Shakir Balogun
- Nigeria Field Epidemiology and Laboratory Training Programme, Abuja 900231, Nigeria;
- African Field Epidemiology Network, Asokoro, Abuja 900231, Nigeria
| | - Hirono Otomaru
- Department of Paediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan (M.T.)
| | - Alash’le Abimiku
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Anthony Agbakizu Ahumibe
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan (H.M.)
- Nigeria Centre for Disease Control and Prevention, Abuja 240102, Nigeria (O.O.); (C.L.O.)
| | - Elsie Ilori
- Nigeria Centre for Disease Control and Prevention, Abuja 240102, Nigeria (O.O.); (C.L.O.)
| | - Que Anh Luong
- Department of Paediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan (M.T.)
| | - Nwando Mba
- Nigeria Centre for Disease Control and Prevention, Abuja 240102, Nigeria (O.O.); (C.L.O.)
| | | | - John Olaide
- Department of Paediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan (M.T.)
| | - Oyeladun Okunromade
- Nigeria Centre for Disease Control and Prevention, Abuja 240102, Nigeria (O.O.); (C.L.O.)
| | - Adama Ahmad
- Nigeria Centre for Disease Control and Prevention, Abuja 240102, Nigeria (O.O.); (C.L.O.)
| | - Afolabi Akinpelu
- Nigeria Centre for Disease Control and Prevention, Abuja 240102, Nigeria (O.O.); (C.L.O.)
| | - Chinwe Lucia Ochu
- Nigeria Centre for Disease Control and Prevention, Abuja 240102, Nigeria (O.O.); (C.L.O.)
| | - Babatunde Olajumoke
- Nigeria Centre for Disease Control and Prevention, Abuja 240102, Nigeria (O.O.); (C.L.O.)
| | - Haruka Abe
- Vietnam Research Station, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan
| | - Chikwe Ihekweazu
- Nigeria Centre for Disease Control and Prevention, Abuja 240102, Nigeria (O.O.); (C.L.O.)
- WHO Hub for Pandemic and Epidemic Intelligence, Prinzessinnenstrasse 17-18, 10969 Berlin, Germany
| | - Adetifa Ifedayo
- Nigeria Centre for Disease Control and Prevention, Abuja 240102, Nigeria (O.O.); (C.L.O.)
- Foundation for Innovative New Diagnostics, 1202 Geneva, Switzerland
| | - Michiko Toizumi
- Department of Paediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan (M.T.)
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki 852-8523, Japan
| | - Hiroyuki Moriuchi
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan (H.M.)
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki 852-8523, Japan
- Department of Paediatrics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan
| | - Katsunori Yanagihara
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan (H.M.)
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki 852-8523, Japan
- Department of Laboratory Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan
| | - Jide Idris
- Nigeria Centre for Disease Control and Prevention, Abuja 240102, Nigeria (O.O.); (C.L.O.)
| | - Lay-Myint Yoshida
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan (H.M.)
- Department of Paediatric Infectious Diseases, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8523, Japan (M.T.)
- School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki 852-8523, Japan
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Boglione L, Crobu MG, Pirisi M, Smirne C. Clinical Characteristics and Outcomes in Patients with Chronic HBV Infection and Hospitalized for COVID-19 Pneumonia: A Retrospective Cohort Study. Viruses 2024; 17:40. [PMID: 39861829 PMCID: PMC11769566 DOI: 10.3390/v17010040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 12/27/2024] [Accepted: 12/27/2024] [Indexed: 01/27/2025] Open
Abstract
The effects of a concomitant infection of hepatitis B virus (HBV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still debated, with a recognized major risk of HBV reactivation during immune-suppressive treatments. The aim of this study was to determine the prevalence and predictive factors of HBV reactivation in a cohort of hospitalized patients with coronavirus disease 2019 (COVID-19) and a current or past hepatitis B infection. In a monocentric retrospective observational study, we enrolled all consecutive hospital admitted patients with COVID-19 pneumonia and a positive HBV serology (N = 84) in our Infectious Diseases Unit from April 2021 to December 2023. We identified 18 (21%) HBsAg-positive/anti-HBc-positive, 41 (49%) HBsAg-negative/anti-HBc-positive/anti-HBs-positive, and 25 (30%) HBsAg-negative/anti-HBc-positive/anti-HBs-negative subjects. The overall rate of hepatitis flare was 10.7%, without any HBsAg seroreversion, severe HBV reactivation, and/or need for new HBV antiviral therapy introduction. Systemic corticosteroid treatment for COVID-19 and baseline anti-HBsAg status were associated with this risk of HBV reactivation. In conclusion, the overall risk of hepatitis flares in hospitalized COVID-19 was reasonably low, with higher doses of corticosteroids treatment being the major risk factor for HBV reactivation, and anti-HBs-positive serological status as a protective element.
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Affiliation(s)
- Lucio Boglione
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (L.B.); (M.P.)
| | - Maria Grazia Crobu
- Laboratory of Molecular Virology, Maggiore della Carità Hospital, 28100 Novara, Italy;
- Clinical Biochemistry Laboratory, City of Health and Science University Hospital, 10126 Turin, Italy
| | - Mario Pirisi
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (L.B.); (M.P.)
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy
| | - Carlo Smirne
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy; (L.B.); (M.P.)
- Internal Medicine Unit, Maggiore della Carità Hospital, 28100 Novara, Italy
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Zhang G, Yan H, Zhang H, Zhu L, Fu J. Drug-induced hepatitis B virus reactivation: insights from FAERS database analysis. Expert Opin Drug Saf 2024:1-6. [PMID: 39630586 DOI: 10.1080/14740338.2024.2438752] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 09/27/2024] [Accepted: 09/30/2024] [Indexed: 12/07/2024]
Abstract
BACKGROUND Reactivation of the hepatitis B virus (HBV) induced by drugs is a commonly overlooked but clinically significant complication, posing risks of treatment interruptions, hepatitis exacerbation, liver failure, and even mortality. METHODS Disproportionality analyses were conducted on the Food and Drug Administration Adverse Event Reporting System (FAERS) database data spanning from January 2017 to December 2023 to detect drugs posing a risk of HBV reactivation (HBV-R). HBV-R cases were identified using the Medical Dictionary for Regulatory Activities (MedDRA), and drug generic names were ascertained from the DrugBank database. RESULTS A total of 2596 adverse event reports (AERs) were found to be related to drug-induced HBV-R.According to the disproportionality analysis, the top five drugs with the highest ROR and PRR were daklinza, vocabria, doxorubicin, sovaldi, and ribavirin. The top 40 drugs causing drug-induced HBV-R can be roughly divided into three categories: anti-tumor drugs, immunosuppressive drugs, and antiviral drugs. Among them, 23 drugs do not explicitly mention the risk of HBV-R in their drug instructions. CONCLUSIONS It was observed that some pharmaceuticals do not adequately address the risk of HBV-R in their drug documentation. These findings could assist healthcare providers in promptly recognizing drug-induced HBV-R.
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Affiliation(s)
- Genshan Zhang
- Department of Gastrointestinal Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hanpeng Yan
- Department of Gastrointestinal Surgery, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Haokun Zhang
- School of Public Health and Health Management, Gannan Medical University, Ganzhou, PR China
| | - Lin Zhu
- Department of Transfusion Medicine, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jie Fu
- Department of Nursing, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Wang J, Wang J, Wang N, Wang W, Zhang P, Lin Y, Li G, Zou Y, Zhong X. Literature review and case study of recurrent EPGA with elevated IgG4 and positive HBsAg successfully treated with rituximab. Ren Fail 2024; 46:2390569. [PMID: 39169678 PMCID: PMC11342811 DOI: 10.1080/0886022x.2024.2390569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 07/23/2024] [Accepted: 08/06/2024] [Indexed: 08/23/2024] Open
Abstract
BACKGROUND Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of autoimmune vasculitis. The involvement of IgG4 and HBsAg in EGPA is less common but can occur and may present unique challenges in management. CASE PRESENTATION We present a case study of a 70-year-old female diagnosed with EGPA confirmed via renal biopsy. She initially presented with recurrent purpura, diarrhea and progressive numbness in the hands and feet, accompanied by general weakness. Complete remission was achieved with a one-year course of prednisone acetate and cyclophosphamide treatment. However, upon discontinuation of self-medication, the disease relapsed, manifesting as a generalized rash and weakness in the extremities.Skin biopsy revealed eosinophil infiltration, with inflammatory cells predominantly surrounding blood vessels. Notably, during treatment, the patient's hepatitis B markers transitioned from negative to positive for HBsAg. Subsequent administration of entecavir, along with monitoring for a decrease in HBV DNA levels, preceded the initiation of steroids and rituximab to attain remission once more. Among the remaining 15 patients analyzed, all exhibited elevated serum IgG4 levels, with none testing positive for hepatitis B. Notably, only one patient was diagnosed with immunoglobulin G4-related disease (IgG4-RD), suggesting that elevated IgG4 levels alone may not necessarily indicate IgG4-RD. CONCLUSIONS Our case report highlights the first instance of recurrent EGPA accompanied by elevated IgG4 and positivity for hepatitis B, which was successfully treated with rituximab. In cases of concurrent hepatitis B, rituximab treatment may be considered once viral replication is under control. However, emphasis on maintenance therapy is crucial following the induction of disease remission.
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Affiliation(s)
- Junru Wang
- Department of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Jun Wang
- Department of Hematology, Chengdu Second People’s Hospital, Chengdu, China
| | - Nan Wang
- Department of Nephrology, Chengdu Second People’s Hospital, Chengdu, China
| | - Wei Wang
- Department of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Ping Zhang
- Department of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yingying Lin
- Department of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Guisen Li
- Department of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yurong Zou
- Department of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiang Zhong
- Department of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
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10
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Hahn NM, Katzin LW. Assessing hepatitis B virus serologies when transitioning patients from intravenous immune globulin therapy to rituximab for the treatment of autoimmune neuromuscular diseases. Muscle Nerve 2024; 70:1040-1045. [PMID: 39267189 DOI: 10.1002/mus.28253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 08/29/2024] [Accepted: 08/30/2024] [Indexed: 09/14/2024]
Abstract
INTRODUCTION/AIMS Intravenous immune globulin (IVIG) has been used as early treatment for autoimmune neuromuscular diseases, but due to cost and frequency, may be switched to rituximab. Rituximab and other B-cell-depleting medications require screening of hepatitis B virus (HBV) serologies given the risk of HBV reactivation (HBVr). We aimed to describe the incidence and characteristics of passively transferred antiviral serologies from IVIG and how to differentiate between passive antibody transfer and resolved HBV infection. METHODS This was a single-center descriptive study of neurology patients prescribed rituximab and IVIG. Retrospective medical record reviews were performed and patient-specific variables were collected. RESULTS Twelve patients had reactive anti-HBc results after starting IVIG, but only 9 were confirmed to have reactive anti-HBc from passive transfer. Whether reactive anti-HBc in the remaining three patients was from passive IVIG transfer could not be confirmed. Five patients with reactive anti-HBc results during rituximab screening did not have pre-IVIG anti-HBc results for comparison and were started on antiviral prophylaxis. Reactive anti-HBc serologies changed to nonreactive after IVIG discontinuation 44-321 days after the last IVIG infusion. DISCUSSION This study confirms IVIG can passively transfer anti-HBc serologies in a neurologic cohort. Ideally, HBV serologies would be checked before starting IVIG to help later determine if passive transfer occurred. With the increasing use of B-cell-depleting medications for neuromuscular conditions, it is important for providers to be knowledgeable on the interpretation of HBV serologies for patients on IVIG and to ensure implementation of an HBVr prophylaxis management strategy for patients when appropriate.
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Affiliation(s)
- Nicole M Hahn
- Pharmacy Department, Kaiser Permanente Colorado, Aurora, Colorado, USA
- Neurology Department, Kaiser Permanente Colorado, Denver, Colorado, USA
| | - Lara W Katzin
- Neurology Department, Kaiser Permanente Colorado, Denver, Colorado, USA
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11
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Belota RCC, Silva JDM, do Nascimento EL, Abrahim CMDM, Castilho MC, Moura Neto JP, Albuquerque SRL. Safety of Hepatitis B Virus Screening in Blood Donors from the Hospital Foundation of Hematology and Hemotherapy of the State of Amazonas (HEMOAM) in the Brazilian Amazon. Viruses 2024; 16:1632. [PMID: 39459965 PMCID: PMC11512298 DOI: 10.3390/v16101632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 10/11/2024] [Accepted: 10/14/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND Hepatitis B is an infectious disease of worldwide importance and of great interest to transfusion medicine. The Amazon region has areas of high endemicity, outlining a worrying scenario for transfusion and epidemiological safety. OBJECTIVE To analyze the profiles of serological and molecular markers for HBV of blood donors from HEMOAM. METHODS Blood donors with different patterns of reactivity in serological and molecular screening for HBV were tested for viral load by the qPCR method at the reference center for liver diseases in the state of Amazonas. RESULTS A total of 230,591 donors were tested, with 3104 (1.34%) found reactive for HBV and 2790 (89.9%) found reactive for isolated anti-HBc. Viral load was not detected in 100% of donors reactive only to HBsAg, while 100% of donors with positive anti-HBc and positive HBsAg or HBV NAT demonstrated a detectable viral load. We also detected one case of occult hepatitis B (0.03%) only with reactive HBV NAT and five donors (0.2%) with positive anti-HBc and HBV NAT. CONCLUSIONS With this result, the great importance of the anti-HBc test for the unsuitability of blood donors was verified, as well as the fundamental introduction of the HBV NAT test in screening for hepatitis B in Brazilian blood banks, as this was the only way to detect the viral infection burden in asymptomatic donors who previously would not be treated, which contributed to the maintenance of the endemicity of hepatitis B in the Brazilian Amazon.
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Affiliation(s)
- Rosa Cristina Caldas Belota
- Programa de Pós-Graduação em Hematologia e Hemoterapia do Amazonas (PPGH/UEA/HEMOAM), Manaus 69050-001, Amazonas, Brazil; (R.C.C.B.); (E.L.d.N.); (C.M.d.M.A.); (J.P.M.N.)
| | - Jean de Melo Silva
- Programa de Pós-Graduação em Imunologia Básica e Aplicada (PPGIBA/UFAM), Manaus 69080-900, Amazonas, Brazil;
| | - Eduardo Luiz do Nascimento
- Programa de Pós-Graduação em Hematologia e Hemoterapia do Amazonas (PPGH/UEA/HEMOAM), Manaus 69050-001, Amazonas, Brazil; (R.C.C.B.); (E.L.d.N.); (C.M.d.M.A.); (J.P.M.N.)
| | - Cláudia Maria de Moura Abrahim
- Programa de Pós-Graduação em Hematologia e Hemoterapia do Amazonas (PPGH/UEA/HEMOAM), Manaus 69050-001, Amazonas, Brazil; (R.C.C.B.); (E.L.d.N.); (C.M.d.M.A.); (J.P.M.N.)
| | - Márcia Costa Castilho
- Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), Manaus 69036-110, Amazonas, Brazil;
| | - José Pereira Moura Neto
- Programa de Pós-Graduação em Hematologia e Hemoterapia do Amazonas (PPGH/UEA/HEMOAM), Manaus 69050-001, Amazonas, Brazil; (R.C.C.B.); (E.L.d.N.); (C.M.d.M.A.); (J.P.M.N.)
- Programa de Pós-Graduação em Imunologia Básica e Aplicada (PPGIBA/UFAM), Manaus 69080-900, Amazonas, Brazil;
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF/UFAM), Manaus 69080-900, Amazonas, Brazil
| | - Sérgio Roberto Lopes Albuquerque
- Programa de Pós-Graduação em Hematologia e Hemoterapia do Amazonas (PPGH/UEA/HEMOAM), Manaus 69050-001, Amazonas, Brazil; (R.C.C.B.); (E.L.d.N.); (C.M.d.M.A.); (J.P.M.N.)
- Programa de Pós-Graduação em Imunologia Básica e Aplicada (PPGIBA/UFAM), Manaus 69080-900, Amazonas, Brazil;
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12
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Xiong D, Cai W, Zhao W. Risk factors of HBV reactivation in leukemia patients with resolved HBV infection after allogeneic hematopoietic stem cell transplantation. Clin Res Hepatol Gastroenterol 2024; 48:102447. [PMID: 39181184 DOI: 10.1016/j.clinre.2024.102447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 08/12/2024] [Accepted: 08/14/2024] [Indexed: 08/27/2024]
Abstract
BACKGROUND The hepatitis B surface antigen (HBsAg)-negative and antibody to hepatitis B core antigen (anti-HBc)-positive patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk of HBV reactivation (HBVr). METHODS To analyze the risk factors for HBVr, a total of 1,042 leukemia patients(≥18years of age), who underwent allo-HSCT from January 2016 to April 2022 in The First Affiliated Hospital of Soochow University, were enrolled in the study. Finally, 193 leukemia patients with resolved HBV infection were included into the study. RESULTS HBVr occurred in 22 patients (11.39 %), and the median time to HBVr was 24 months (with a range of 11-51months). Hepatitis flares developed in 22.73 % of patients with HBVr, and hepatic failure occurred in 1 patient. During the follow-up period, only 1(1.3 %) patient experienced HBVr among 79 patients with antiviral prophylaxis. While 21(18.42 %) patients experienced HBVr among 114 patients without antiviral prophylaxis. The cumulative incidence of HBV reactivation at 3 years was 44.4. % for anti-HBs-negative donors/recipients with a low anti-HBs titer (<100IU/L) and 7.1 % for anti-HBs-positive donors/recipients with a high anti-HBs titer (≥100IU/L) respectively. In addition, univariate and multivariate Cox regression analyses confirmed the use of rituximab as a risk factor for HBV reactivation. CONCLUSION The univariate and multivariate analyses confirmed that the anti-HBs titer in both recipients and donors are protective indicators to prevent incidence of HBVr. In addition, antiviral prophylaxis can significantly reduce the incidence of HBVr.
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Affiliation(s)
- Danping Xiong
- Department of Infection Diseases, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Wen Cai
- Department of Infection Diseases, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Weifeng Zhao
- Department of Infection Diseases, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
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13
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Sohal A, Singh C, Bhalla A, Kalsi H, Roytman M. Renal Manifestations of Chronic Hepatitis C: A Review. J Clin Med 2024; 13:5536. [PMID: 39337023 PMCID: PMC11433393 DOI: 10.3390/jcm13185536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2024] [Revised: 09/13/2024] [Accepted: 09/16/2024] [Indexed: 09/30/2024] Open
Abstract
Hepatitis C virus (HCV) has emerged as a major global health concern and, if left untreated, can lead to significant liver damage, including cirrhosis, decompensated liver disease, and hepatocellular carcinoma (HCC). Approximately 40% of patients with HCV infection experience extrahepatic manifestations, including renal involvement. HCV-related renal disease is of significant importance among patients with chronic kidney disease (CKD), leading to higher morbidity and mortality. The renal damage due to HCV infection primarily results from cryoglobulinemia and glomerulonephritis, with conditions such as membranoproliferative glomerulonephritis (MPGN) and membranous nephropathy (MN) being most prevalent. Despite advancements in treatment, including the use of directly acting antiviral agents (DAAs), renal complications remain a significant burden in untreated patients. HCV-positive patients on hemodialysis (HD) or those who have undergone kidney transplantation face increased mortality rates compared to their HCV-negative counterparts. Managing HCV infection before kidney transplantation is crucial to mitigate the risk of HCV-related renal complications. Conversely, kidney transplantation from HCV-infected donors is well established, as post-transplant treatment for HCV is safe and effective, potentially reducing mortality and morbidity for patients on transplant waiting lists. This review aims to provide a comprehensive analysis of the renal manifestations of HCV, emphasizing the importance of early diagnosis and treatment to improve patient outcomes.
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Affiliation(s)
- Aalam Sohal
- Division of Gastroenterology and Hepatology, Creighton University School of Medicine, Phoenix, AZ 2500, USA
| | - Carol Singh
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
| | - Akshita Bhalla
- Department of Internal Medicine, Punjab Institute of Medical Sciences, Jalandhar 144006, Punjab, India
| | - Harsimran Kalsi
- Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL 32827, USA
| | - Marina Roytman
- Division of Gastroenterology and Hepatology, University of California San Francisco, Fresno, CA 93701, USA
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14
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Sasaki T, Kakisaka K, Miyasaka A, Nishiya M, Yanagawa N, Kuroda H, Matsumoto T, Takahashi M, Okamoto H. Spontaneous reactivation of hepatitis B virus with multiple novel mutations in an elderly patient with resolved hepatitis B virus infection. Clin J Gastroenterol 2024; 17:683-690. [PMID: 38748198 DOI: 10.1007/s12328-024-01984-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 05/05/2024] [Indexed: 07/11/2024]
Abstract
Spontaneous reactivation of the Hepatitis B virus (HBV) is rare in individuals with previously resolved infections. This report presents the case of a 71 year-old Japanese woman who experienced HBV reactivation without any prior immunosuppressive therapy or chemotherapy. Before the onset of liver injury, the patient was negative for hepatitis B surface antigen (HBsAg) but positive for hepatitis B surface antibody. She subsequently developed liver injury, with the reappearance of HBsAg and HBV DNA. The patient was successfully treated with tenofovir alafenamide, and prednisolone. Full-genome sequencing of HBV revealed subgenotype B1 without hepatitis B e-negative mutations in the precore and core promoter regions and 12 amino acid alterations in the pre-S1/S, P, and X genes. Notably, the S gene mutations D144A and K160N, which alter the antigenicity of HBsAg and potentially contribute to its reactivation, were identified. This case emphasizes the importance of vigilance for spontaneous reactivation of resolved HBV, highlighting the need for comprehensive genomic analysis to understand the associated virological intricacies.
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Affiliation(s)
- Tokio Sasaki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Iwate, 028-3694, Japan.
| | - Keisuke Kakisaka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Iwate, 028-3694, Japan
| | - Akio Miyasaka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Iwate, 028-3694, Japan
| | - Masao Nishiya
- Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Iwate, 028-3694, Japan
| | - Naoki Yanagawa
- Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Iwate, 028-3694, Japan
| | - Hidekatsu Kuroda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Iwate, 028-3694, Japan
| | - Takayuki Matsumoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Iwate, 028-3694, Japan
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
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15
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Savaliya BP, Shekouhi R, Mubarak F, Manaise HK, Jimenez PB, Kowkabany G, Popp RA, Popp K, Gabriel E. Risk of hepatitis B virus reactivation in cancer patients undergoing treatment with tyrosine kinase-inhibitors. World J Gastroenterol 2024; 30:3052-3058. [PMID: 38983963 PMCID: PMC11230056 DOI: 10.3748/wjg.v30.i24.3052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 05/10/2024] [Accepted: 05/30/2024] [Indexed: 06/25/2024] Open
Abstract
This editorial commented on an article in the World Journal of Gastroenterology titled "Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors: Case Report and Literature Analysis" by Colapietro et al. In this editorial, we focused on providing a more comprehensive exploration of hepatitis B virus reactivation (HBVr) associated with the usage of tyrosine kinase inhibitors (TKIs). It includes insights into the mechanisms underlying HBV reactivation, the temporal relationship between TKIs and HBV reactivation, and preventive measures. The aim is to understand the need for nucleos(t)ide analogs (NAT) and serial blood tests for early recognition of reactivation and acute liver injury, along with management strategies. TKIs are considered to be an intermediate (1%-10%) of HBVr. Current guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen, anti-hepatitis B core antigen (HBc), and anti-hepatitis B surface antibody. Anti-HBc screening in highly endemic areas means people with negative tests should be vaccinated against HBV. Nucleoside or nucleotide analogs (NAs) like entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) form the basis of HBV reactivation prophylaxis and treatment during immunosuppression. Conversely, lamivudine, telbivudine, and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral strains. However, these less effective NAs may still be utilized in cases where ETV, TDF, and TAF are not feasible treatment options.
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Affiliation(s)
- Bansi P Savaliya
- Department of Surgery, Medical Academy Named after SI Georgievsky of Vernadsky Crimean Federal University, Simferopol 295015, Crimea, Russia
| | - Ramin Shekouhi
- Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Florida, Gainesville, FL 32608, United States
| | - Fatima Mubarak
- Department of Surgery, Aga Khan University, Karachi 74800, Sindh, Pakistan
| | - Harsheen K Manaise
- Department of Surgery, Government Medical College and Hospital, Chandigarh 160030, Punjab, India
| | - Paola Berrios Jimenez
- Department of Surgery, University of Puerto Rico School of Medicine, San Juan 00921, Puerto Rico
| | - Gabrielle Kowkabany
- Department of Chemical and Biological Engineering, University of Alabama, Tuscaloosa, AL 35487, United States
| | - Reed A Popp
- Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Kyle Popp
- Department of Surgery, Florida State University, Tallahassee, FL 32306, United States
| | - Emmanuel Gabriel
- Department of Surgery, Mayo Clinic, Jacksonville, FL 32224, United States
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16
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Chang MH, Guo Y, Acbo A, Bao H, McSweeney T, Vo CA, Nori P. Antiretroviral Stewardship: Top 10 Questions Encountered by Stewardship Teams and Solutions to Optimize Therapy. Clin Ther 2024; 46:455-462. [PMID: 38704295 DOI: 10.1016/j.clinthera.2024.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Revised: 03/26/2024] [Accepted: 04/04/2024] [Indexed: 05/06/2024]
Abstract
PURPOSE Infectious disease pharmacists and physicians overseeing antimicrobial stewardship programs possess expertise and often advanced certification in management of antiretrovirals to treat HIV. Stewardship programs are responsible for managing facility formularies and must stay up to date with the latest antiretrovirals, including once daily formulations and depot injectables. Furthermore, stewardship program members need to understand drug-interactions, short-, and long-term toxicities of these regimens, including dyslipidemia and cardiovascular effects. Patients receiving chronic antiretroviral therapy may present to the acute care, ambulatory care, and long-term care settings. Like other antimicrobials, audit-and-feedback, drug monitoring, and dose-optimization are often required to prevent antiretroviral associated medication errors and minimize resistance. METHODS A narrative review was conducted on antiretroviral stewardship, addressing common clinical questions encountered by stewardship teams and best practices to optimize antiretroviral therapy and reduce the risk for treatment interruptions, resistance, drug interactions, long term toxicities, and other adverse effects. FINDINGS People living with HIV are often hospitalized and treated by medical teams without formal HIV training. For this reason, these patients are at greater risk for medication errors during hospitalization and between transitions of care. Many opportunities are present for antiretroviral stewardship to mitigate these errors. Frequent updates to simplify HIV regimen, maintain select patients on fixed-dose combination tablets, and strategies to minimize drug interactions make it difficult for even the seasoned clinician to keep up regularly. IMPLICATIONS Despite the availability of free online HIV resources and progress made in HIV management, significant opportunities for antiretroviral stewardship remain. Implementing electronic order entry updates, formulary upgrades, and formal pharmacy renal dose adjustments to optimize antiretroviral therapy will help clinicians harness these opportunities. Dedicated time and expertise for antiretroviral stewardship as part of local antimicrobial stewardship programs are needed.
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Affiliation(s)
- Mei H Chang
- Department of Pharmacy, Montefiore Health System, Bronx, New York.
| | - Yi Guo
- Department of Pharmacy, Montefiore Health System, Bronx, New York
| | - Antoinette Acbo
- Department of Pharmacy, Montefiore Health System, Bronx, New York
| | - Hongkai Bao
- Department of Pharmacy, Montefiore Health System, Bronx, New York
| | | | - Christopher A Vo
- Division of Infectious Diseases, Department of Medicine, Montefiore Health System, Albert Einstein College of Medicine, Bronx, New York
| | - Priya Nori
- Division of Infectious Diseases, Department of Medicine, Montefiore Health System, Albert Einstein College of Medicine, Bronx, New York
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17
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Cohen EB, Regev A, Garg A, Di Bisceglie AM, Lewis JH, Vierling JM, Hey-Hadavi J, Steplewski K, Fettiplace A, Chen CL, Pehlivanov N, Kendrick S, I Avigan M. Consensus Guidelines: Best Practices for the Prevention, Detection and Management of Hepatitis B Virus Reactivation in Clinical Trials with Immunosuppressive/Immunomodulatory Therapy. Drug Saf 2024; 47:321-332. [PMID: 38353882 PMCID: PMC10954982 DOI: 10.1007/s40264-024-01399-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2024] [Indexed: 03/21/2024]
Abstract
Hepatitis B virus reactivation (HBVr) during and after immunosuppressive/immunomodulatory (IS/IM) therapy is associated with significant morbidity and mortality, including hepatic decompensation and acute liver failure. The risk of HBVr with IS/IM has been heterogeneous and often unpredictable. As a result, patients with active or previous HBV infection are often excluded from clinical drug trials of such agents. Thorough screening for HBV infection, antiviral prophylaxis, and careful monitoring for HBVr have proven to be effective in reducing the rate of HBVr and improving its outcome in the context of IS/IM. Therefore, safe enrollment and management of certain HBV-marker-positive patients in clinical trials is possible. There is a great, unmet need for consistent, evidence-based recommendations for best practices pertaining to enrollment, monitoring, and management of HBVr in clinical trial participants receiving IS/IM. The aim of these consensus guidelines is to provide a step-by-step blueprint to safely enroll, monitor and manage the patient with inactive chronic or resolved HBV in IS/IM clinical trials from the time of screening through to the end of post-treatment follow up.
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Affiliation(s)
- Eric B Cohen
- AbbVie Inc., Pharmacovigilance and Patient Safety, North Chicago, IL, USA.
| | - Arie Regev
- Eli Lilly and Company, Global Patient Safety, Indianapolis, IN, USA
| | - Anju Garg
- Sanofi, Patient Safety & Pharmacovigilance, Bridgewater, NJ, USA
| | | | - James H Lewis
- Division of Gastroenterology, Georgetown University, Washington, DC, USA
| | - John M Vierling
- Section of Gastroenterology and Hepatology and Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, USA
| | | | - Klaudia Steplewski
- GlaxoSmithKline LLC, Clinical Safety and Pharmacovigilance, Collegeville, PA, USA
| | | | - Chunlin L Chen
- Bayer HealthCare Pharmaceuticals, LLC. Pharmacovigilance, Berlin, Germany
| | - Nonko Pehlivanov
- Merck & Co., INC, Clinical Safety Risk Management, Rahway, NJ, USA
| | - Stuart Kendrick
- GlaxoSmithKline LLC, Medical Affairs-Hepatology, Stevenage, UK
| | - Mark I Avigan
- Food and Drug Administration, Center for Drug Evaluation and Research, Silver Spring, MD, USA
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18
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Sudevan N, Manrai M, Tilak TVSVGK, Khurana H, Premdeep H. Chronic hepatitis B and occult infection in chemotherapy patients - evaluation in oncology and hemato-oncology settings: The CHOICE study. World J Virol 2024; 13:89104. [PMID: 38616860 PMCID: PMC11008399 DOI: 10.5501/wjv.v13.i1.89104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 12/27/2023] [Accepted: 01/24/2024] [Indexed: 03/11/2024] Open
Abstract
BACKGROUND Reactivation of hepatitis B virus (HBV) infection is a well-known risk that can occur spontaneously or following immunosuppressive therapies, including cancer chemotherapy. HBV reactivation can cause significant morbidity and even mortality, which are preventable if at-risk individuals are identified through screening and started on antiviral prophylaxis. AIM To determine the prevalence of chronic HBV (CHB) and occult HBV infection (OBI) among oncology and hematology-oncology patients undergoing chemotherapy. METHODS In this observational study, the prevalence of CHB and OBI was assessed among patients receiving chemotherapy. Serological markers of HBV infection [hepatitis B surface antigen (HBsAg)/anti-hepatitis B core antigen (HBc)] were evaluated for all patients. HBV DNA levels were assessed in those who tested negative for HBsAg but positive for total anti-HBc. RESULTS The prevalence of CHB in the study cohort was determined to be 2.3% [95% confidence interval (95%CI): 1.0-4.2]. Additionally, the prevalence of OBI among the study participants was found to be 0.8% (95%CI: 0.2-2.3). CONCLUSION The findings of this study highlight the importance of screening for hepatitis B infection in oncology and hematology-oncology patients undergoing chemotherapy. Identifying individuals with CHB and OBI is crucial for implementing appropriate antiviral prophylaxis to prevent the reactivation of HBV infection, which can lead to increased morbidity and mortality.
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Affiliation(s)
- Nayana Sudevan
- Department of Internal Medicine, Armed Forces Medical College, Pune 411040, India
| | - Manish Manrai
- Department of Gastroenterology, Command Hospital Cantonment Rd, Sadar Bazaar, Cantonment, Lucknow, Uttar Pradesh, India 226002
| | - T V S V G K Tilak
- Department of Internal Medicine, Command Hospital, Bangalore 560007, India
| | - Harshit Khurana
- Department of Geriatric Medicine, Armed Forces Medical College, Pune 411040, India
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19
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De Pauli S, Grando M, Miotti G, Zeppieri M. Hepatitis B virus reactivation in patients treated with monoclonal antibodies. World J Virol 2024; 13:88487. [PMID: 38616853 PMCID: PMC11008406 DOI: 10.5501/wjv.v13.i1.88487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 11/23/2023] [Accepted: 12/19/2023] [Indexed: 03/11/2024] Open
Abstract
Hepatitis B virus (HBV) reactivation poses a significant clinical challenge, especially in patients undergoing immunosuppressive therapies, including monoclonal antibody treatments. This manuscript briefly explores the complex relationship between monoclonal antibody therapy and HBV reactivation, drawing upon current literature and clinical case studies. It delves into the mechanisms underlying this phenomenon, highlighting the importance of risk assessment, monitoring, and prophylactic measures for patients at risk. The manuscript aims to enhance the understanding of HBV reactivation in the context of monoclonal antibody therapy, ultimately facilitating informed clinical decision-making and improved patient care. This paper will also briefly review the definition of HBV activation, assess the risks of reactivation, especially in patients treated with monoclonal antibodies, and consider management for patients with regard to screening, prophylaxis, and treatment. A better understanding of patients at risk can help clinicians provide optimum management to ensure successful patient outcomes and prevent morbidity.
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Affiliation(s)
- Silvia De Pauli
- Department of Internal Medicine, Azienda Sanitaria Friuli Occidentale, San Vito al Tagliamento, Pordenone 33170, Italy
| | - Martina Grando
- Department of Internal Medicine, Azienda Sanitaria Friuli Occidentale, San Vito al Tagliamento, Pordenone 33170, Italy
| | - Giovanni Miotti
- Department of Plastic Surgery, University Hospital of Udine, Udine 33100, Italy
| | - Marco Zeppieri
- Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
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Zeng Y, Huang J, Pang J, Pan S, Wu Y, Jie Y, Li X, Chong Y. The occurrence of immune-related adverse events is an independent risk factor both for serum HBsAg increase and HBV reactivation in HBsAg-positive cancer patients receiving PD-1 inhibitor combinational therapy. Front Immunol 2024; 15:1330644. [PMID: 38558804 PMCID: PMC10979302 DOI: 10.3389/fimmu.2024.1330644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 02/20/2024] [Indexed: 04/04/2024] Open
Abstract
BACKGROUND Previous studies have suggested the potential of PD-1/PD-L1 inhibitors in the treatment of chronic HBV infection. However, since phase III clinical trials have not yet been announced, additional clinical insights may be obtained by observing changes in serum hepatitis B surface antigen (HBsAg) and HBV-DNA levels in cancer patients undergoing PD-1 inhibitor therapy. OBJECTIVE To explore the effects of PD-1 inhibitor combinational therapy on serum HBsAg and HBV-DNA levels, investigate the incidence of HBsAg loss, HBV reactivation (HBVr), and immune-related adverse events (irAEs), and identify the risk factors associated with significant HBsAg fluctuations and HBVr. METHODS A retrospective study including 1195 HBsAg-positive cancer patients who received PD-1 inhibitors between July 2019 and June 2023 was conducted, and 180 patients were enrolled in this study. Serum HBsAg levels before and after PD-1 inhibitor administration were compared across different subgroups. The Pearson χ2 or Fisher exact test was performed to investigate the relationships between categorical variables. Univariable and multivariable analysis were performed to identify the risk factors associated with significant HBsAg fluctuations and HBVr. RESULTS With the concurrent use of antiviral agents, serum HBsAg levels decreased (Z=-3.966, P < 0.0001) in 129 patients and increased (t=-2.047, P=0.043) in 51 patients. Additionally, 7 patients (3.89%) achieved serum HBsAg loss. Virus replication was suppressed in most of the enrolled patients. When divided patients into different subgroups, significant HBsAg decreases after PD-1 inhibitor administration were discovered in lower baseline HBsAg group (Z=-2.277, P=0.023), HBeAg-seronegative group (Z=-2.200, P=0.028), non-irAEs occurrence group (Z=-2.007, P=0.045) and liver cancer group (Z=-1.987, P=0.047). Of note, 11 patients and 36 patients experienced HBVr (6.11%) and irAEs (20%), respectively, which could lead to discontinuation or delayed use of PD-1 inhibitors. After multivariable analysis, HBeAg-seropositive (OR, 7.236 [95% CI, 1.757-29.793], P=0.01) and the occurrence of irAEs (OR, 4.077 [95% CI, 1.252-13.273], P=0.02) were identified as the independent risk factors for significant HBsAg increase, the occurrence of irAEs (OR, 5.560 [95% CI, 1.252-13.273], P=0.01) was identified as the only independent risk factor for HBVr. CONCLUSION PD-1 inhibitors combined with nucleos(t)ide analogues (NAs) may exert therapeutic potential for chronic HBV infection in cancer patients. However, attention also should be paid to the risk of significant elevation in HBsAg levels, HBVr, and irAEs associated with PD-1 inhibitor combinational therapy.
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Affiliation(s)
- Yingfu Zeng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jiwei Huang
- Department of Pharmacy, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jiahui Pang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shufang Pan
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yuankai Wu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yusheng Jie
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xinhua Li
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yutian Chong
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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21
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Vyas Y, Tsai NC, Katz AR, Pham T. Hepatitis B Prevalence and Risk Factors in Foreign-Born Asians and Pacific Islanders at a Federally Qualified Health Center in Hawai'i, 2015-2020. HAWAI'I JOURNAL OF HEALTH & SOCIAL WELFARE 2024; 83:48-53. [PMID: 38344695 PMCID: PMC10850867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 02/15/2024]
Abstract
The objective of this study was to estimate the prevalence of chronic hepatitis B infection in foreign-born Asians and Pacific Islanders at Kalihi-Palama Health Center in Honolulu, Hawai'i, and to assess the association between both chronic and resolved hepatitis B infection and risk factors such as household exposure to hepatitis B virus and geographic location of birthplace. The study involved cross-sectional data from 997 participants who accessed medical services at Kalihi-Palama Health Center between September 2015 and July 2020. The prevalence of chronic hepatitis B was 10.7%. On multivariable logistic regression analysis, the adjusted prevalence odds ratio of chronic hepatitis B infection was 3.3 times greater (95% confidence interval: 1.1, 9.2) for those who reported household contact with a person with hepatitis B infection than those who reported no such contact. No association was found with place of birth in this study population. Age was a significant predictor of chronic hepatitis B, with participants between 35-44 years of age having the highest prevalence. Age was also a significant predictor of resolved hepatitis B infection, with participants 65 years of age or older having the highest prevalence. These findings emphasize the need for targeted screening and appropriate follow-up-including vaccination or treatment-in this at-risk population.
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Affiliation(s)
| | - Naoky C. Tsai
- John A. Burns School of Medicine, University of Hawai‘i, Honolulu, HI (NCT)
| | - Alan R. Katz
- Office of Public Health Studies, Thompson School of Social Work and Public Health, University of Hawai‘i, Honolulu, HI (ARK)
| | - Thaddeus Pham
- Harm Reduction Services Branch, Communicable Disease and Public Health Nursing Division, Hawai‘i Department of Health, Honolulu, HI (TP)
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Anvari S, Tsoi K. Hepatitis B Virus Reactivation with Immunosuppression: A Hidden Threat? J Clin Med 2024; 13:393. [PMID: 38256527 PMCID: PMC10816226 DOI: 10.3390/jcm13020393] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 12/23/2023] [Accepted: 01/09/2024] [Indexed: 01/24/2024] Open
Abstract
Hepatitis B virus (HBV) reactivation in the setting of immunosuppressive therapy is an increasingly recognized and preventable cause of elevated liver enzymes and clinical hepatitis in treated patients. However, not all immunosuppressive therapies confer the same risk. The purpose of this article was to review the literature on risks of HBV reactivation associated with immunosuppressive agents and propose a management algorithm. We searched Google Scholar, PubMed, and MEDLINE for studies related to hepatitis B reactivation and various immunosuppressive agents. The risk of HBV reactivation was found to differ by agent and depending on whether a patient had chronic HBV (HBsAg+) or past HBV (HBsAg-, anti-HBc+). The highest risk of reactivation (>10%) was associated with anti-CD20 agents and hematopoietic stem cell transplants. Multiple societies recommend HBV-specific anti-viral prophylaxis for patients with positive HBsAg prior to the initiation of immunosuppressive therapy, while the guidance for HBsAg- patients is more variable. Clinicians should check HBV status prior to beginning an immune-suppressive therapy. Patients with positive HBsAg should be initiated on antiviral prophylaxis in the majority of cases, whereas HBsAg- individuals should be evaluated on a case-by-case basis. Further research is required to determine the optimum duration of therapy.
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Affiliation(s)
- Sama Anvari
- Division of Gastroenterology, Department of Internal Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada;
- Division of Gastroenterology, St. Joseph’s Healthcare Hamilton, Hamilton, ON L8N 4A6, Canada
| | - Keith Tsoi
- Division of Gastroenterology, Department of Internal Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada;
- Division of Gastroenterology, St. Joseph’s Healthcare Hamilton, Hamilton, ON L8N 4A6, Canada
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Chen HL, Jourdain G. Prevention of HBV infection. Clin Liver Dis (Hoboken) 2024; 23:e0194. [PMID: 38872782 PMCID: PMC11168846 DOI: 10.1097/cld.0000000000000194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 03/25/2024] [Indexed: 06/15/2024] Open
Affiliation(s)
- Huey-Ling Chen
- Department of Pediatrics, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan
- Department and Graduate Institute of Medical Education and Bioethics, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Gonzague Jourdain
- Department of PHPT Research Collaboration, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand
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Unver Ulusoy T, Tıglıoglu P, Demirköse H, Albayrak M, Şencan İ. Change in Hepatitis B Surface Antibody Titers After Chemotherapy in Patients With Hematological Malignancies. Cureus 2024; 16:e51572. [PMID: 38314000 PMCID: PMC10836041 DOI: 10.7759/cureus.51572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/02/2024] [Indexed: 02/06/2024] Open
Abstract
Background The change in hepatitis B surface antibody (anti-HBs) titers after chemotherapy (CT) in patients with hematological malignancy, affecting factors, and its clinical implications have not been sufficiently understood. Therefore, we aim to evaluate the change in anti-HBs titers and hepatitis B virus reactivation (HBVr) after CT. Methods This retrospective study enrolled patients with hematological malignancies who received CT between 2013 and 2021. All patients were followed up for HBVr and a change in anti-HBs titers for one year. Results Overall, 192 patients were included. In total, 33.9% of the patients were anti-HBs (+) and 26% of the patients were anti-HBc (+) ± anti-HBs (+). Hepatitis B virus (HBV) prophylaxis was given to 35 (70%) of 50 Anti-HBc (+) patients. Tenofovir disoproxil fumarate and entecavir prophylaxis were initiated in 25 (71.4%) and 10 (28.6%) patients, respectively. A significant decrease was found in anti-HBs titers of all patients (p=0.017). A significant decrease was also found in anti-HBs titers of HBc IgG (+) patients and those who received four or more courses of CT (p=0.025; p=0.041). HBVr was not diagnosed in any of the patients. Conclusion Chemotherapeutic agents administered for hematological malignancy have serious immunosuppression effects. In these patients, anti-HBs titers may decrease or become negative one year after CT. Anti-HBs titer before CT or its change after CT may not constitute a risk for HBVr patients who received HBV prophylaxis in line with current guidelines and these recommendations.
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Affiliation(s)
- Tülay Unver Ulusoy
- Department of Infectious Diseases and Clinical Microbiology, Ankara Etlik City Hospital, Ankara, TUR
- Department of Infectious Diseases and Clinical Microbiology, Dışkapı Yildirim Beyazit Training and Research Hospital, University of Health Sciences, Ankara, TUR
| | - Pınar Tıglıoglu
- Department of Hematology, Dr. Ersin Arslan Training and Research Hospital, Gaziantep, TUR
| | - Hacer Demirköse
- Department of Public Health, Pursaklar District Health Directorate, Ankara, TUR
| | - Murat Albayrak
- Department of Haematology, Ankara Etlik City Hospital, Ankara, TUR
| | - İrfan Şencan
- Department of Infectious Diseases and Clinical Microbiology, Dışkapı Yildirim Beyazit Training and Research Hospital, University of Health Sciences, Ankara, TUR
- Department of Infectious Diseases and Clinical Microbiology, Ankara Etlik City Hospital, Ankara, TUR
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Yuan GC, Chen AZ, Wang WX, Yi XL, Tu L, Peng F, Qiu ZH. Efficacy and safety of tenofovir alafenamide in patients with chronic hepatitis B exhibiting suboptimal response to entecavir. World J Clin Cases 2023; 11:8139-8146. [PMID: 38130795 PMCID: PMC10731186 DOI: 10.12998/wjcc.v11.i34.8139] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 11/23/2023] [Accepted: 11/28/2023] [Indexed: 12/06/2023] Open
Abstract
BACKGROUND Entecavir (ETV) is a potent and safe antiviral agent for patients with chronic hepatitis B (CHB); however, some patients may exhibit suboptimal response or resistance to ETV. Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil fumarate. AIM To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to ETV. METHODS A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia [Hepatitis B virus (HBV) DNA ≥ 20 IU/mL] or partial virologic response (HBV DNA < 20 IU/mL, but detectable) were enrolled in the study. The patients were randomly assigned to either continue ETV (0.5 mg) daily or switch to TAF (25 mg) daily for 48 wk. The primary endpoint was the proportion of patients who achieved a virologic response (HBV DNA level < 20 IU/mL) at week 48. Secondary endpoints included changes in serum alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and anti-HBe levels, and renal and bone safety parameters. RESULTS At week 48, the proportion of patients who achieved a virologic response was significantly higher in the TAF group than in the ETV group (93.3% vs 66.7%, P = 0.012). The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group (-3.8 vs -2.4 Log10 IU/mL, P < 0.001). The rates of ALT normalization, HBeAg loss, HBeAg seroconversion, and HBsAg loss were not found to significantly differ between the two groups. None of the patients developed genotypic resistance to ETV or TAF. Both drugs were well tolerated, with no serious adverse events or discontinuations caused by adverse events. No significant changes were observed in the estimated glomerular filtration rate, serum creatinine level, or urine protein-to-creatinine ratio in either group. The TAF group had a significantly lower decrease in bone mineral density at the lumbar spine and hip than the ETV group (-0.8% vs -2.1%, P = 0.004; -0.6% vs -1.8%, P = 0.007, respectively). CONCLUSION Switching from ETV to TAF is effective and safe for patients with CHB exhibiting a suboptimal response to ETV and may prevent further viral resistance and reduce renal and bone toxicity.
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Affiliation(s)
- Gui-Cai Yuan
- Department of Infectious Diseases, Yichun University Second Affiliated Hospital, Yichun 336000, Jiangxi Province, China
| | - Ai-Zhen Chen
- Department of Infectious Diseases, Yichun University Second Affiliated Hospital, Yichun 336000, Jiangxi Province, China
| | - Wei-Xin Wang
- Department of Infectious Diseases, Yichun University Second Affiliated Hospital, Yichun 336000, Jiangxi Province, China
| | - Xu-Lan Yi
- Department of Infectious Diseases, Yichun University Second Affiliated Hospital, Yichun 336000, Jiangxi Province, China
| | - Long Tu
- Department of Infectious Diseases, Yichun University Second Affiliated Hospital, Yichun 336000, Jiangxi Province, China
| | - Fang Peng
- Department of Infectious Diseases, Yichun University Second Affiliated Hospital, Yichun 336000, Jiangxi Province, China
| | - Zhi-Hong Qiu
- Department of Infectious Diseases, Yichun University Second Affiliated Hospital, Yichun 336000, Jiangxi Province, China
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Shoraka S, Mohebbi SR, Hosseini SM, Ghaemi A, Zali MR. SARS-CoV-2 and chronic hepatitis B: Focusing on the possible consequences of co-infection. JOURNAL OF CLINICAL VIROLOGY PLUS 2023; 3:100167. [DOI: 10.1016/j.jcvp.2023.100167] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
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Katelani S, Fragoulis GE, Bakasis AD, Pouliakis A, Nikiphorou E, Atzeni F, Androutsakos T. HBV reactivation in patients with rheumatoid arthritis treated with anti-interleukin-6: a systematic review and meta-analysis. Rheumatology (Oxford) 2023; 62:SI252-SI259. [PMID: 37871924 DOI: 10.1093/rheumatology/kead243] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 04/23/2023] [Indexed: 10/25/2023] Open
Abstract
OBJECTIVE The objective of this study was to assess the possibility of HBV reactivation (HBVr) in patients with RA under anti-IL-6 treatment. METHODS Using PubMed, Scopus and EMBASE, we performed a systematic literature search for articles related to HBVr in RA patients under anti-IL-6 treatment. The search was performed with no date limits and was last updated 28 January 2023. The results from all the databases were combined and duplicates were excluded, as were non-English articles, case reports, position articles, comments, and paediatric studies. RESULTS Our initial search led to 427 articles; 28 were duplicates, 46 non-English, 169 reviews, 31 books/letters, 25 case reports, and 88 irrelevant to the meta-analysis aim; 21 were excluded due to inadequate information, leaving 19 articles, with a sum of 372 RA patients with chronic HBV (CHB) or resolved HBV infection, for further analysis. The overall risk for HBVr in RA patients with CHB was 6.7%, increasing to 37% when only RA patients with CHB and no antiviral prophylaxis were included. On the contrary, HBVr was close to 0% in RA patients with resolved HBV infection, irrespective of antiviral prophylaxis. All RA patients experiencing HBVr in these studies were successfully managed with antiviral treatment and/or drug withdrawal. CONCLUSION Overall, anti-IL-6 treatment comes with a significant risk of HBVr in RA patients with CHB; risk is diminished when antiviral prophylaxis is used. In contrast, in RA patients with resolved HBV infection, the risk of HBVr seems to be extremely low. Large, well-designed studies (either controlled trials or multicentre/international observational studies) are warranted to further validate these results.
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Affiliation(s)
- Stamatia Katelani
- Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - George E Fragoulis
- First Department of Internal Medicine, Propedeutic Clinic, "Laiko" Hospital, National and Kapodistrian University of Athens, Athens, Greece
- Institute of Infection, Immunity and Inflammation, University of Glasgow, Scotland, UK
| | | | - Abraham Pouliakis
- 2nd Department of Pathology, National and Kapodistrian University of Athens, Medical School, University General Hospital Attikon, Athens, Greece
| | - Elena Nikiphorou
- Centre for Rheumatic Diseases, King's College London, London, UK
| | - Fabiola Atzeni
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina, Messina, Italy
| | - Theodoros Androutsakos
- Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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Rzymski P, Zarębska-Michaluk D, Flisiak R. Could chronic HBV infection explain Beethoven's hearing loss? Implications for patients currently living with hepatitis B. J Infect 2023; 87:171-176. [PMID: 37302659 DOI: 10.1016/j.jinf.2023.06.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/01/2023] [Accepted: 06/06/2023] [Indexed: 06/13/2023]
Abstract
The cause of Ludwig van Beethoven's health deterioration, i.e., hearing loss and cirrhosis, have been subject to various studies. The genomic analysis of his hair indicates infection with the hepatitis B virus (HBV) at least 6 months prior to death. However, considering his first documented case of jaundice in the summer of 1821, second jaundice months prior to his death, and increased risk of hearing loss in HBV-infected patients, we offer an alternative hypothesis of chronic HBV infection as a cause of deafness and cirrhosis. According to it, HBV was acquired early, progressed from immune-tolerant to an immune-reactive phase, and triggered Beethoven's hearing issues when aged 28. Later, HBV infection entered the non-replication phase with at least two episodes of reactivation in the fifth decade of life accompanied by jaundice. More studies examining hearing loss in patients with chronic HBV infection are encouraged to better understand their potential otologic needs.
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Affiliation(s)
- Piotr Rzymski
- Department of Environmental Medicine, Poznan University of Medical Sciences, 60-806 Poznań, Poland.
| | - Dorota Zarębska-Michaluk
- Department of Infectious Diseases and Allergology, Jan Kochanowski University, 25-317 Kielce, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-540 Białystok, Poland
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Li F, Wang T, Tang F, Liang J. Fatal acute-on-chronic liver failure following camrelizumab for hepatocellular carcinoma with HBsAg seroclearance: a case report and literature review. Front Med (Lausanne) 2023; 10:1231597. [PMID: 37644988 PMCID: PMC10461443 DOI: 10.3389/fmed.2023.1231597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 07/24/2023] [Indexed: 08/31/2023] Open
Abstract
In the last few years, immune checkpoint inhibitors (ICIs) have become major therapeutic agents for the treatment of advanced hepatocellular carcinoma (HCC). However, immunotherapy can activate hepatitis B virus (HBV), and immune clearance may lead to liver failure and even life-threatening conditions. Here we report a case of HCC with HBV-related cirrhosis that caused severe liver injury and rapidly progressed to fatal acute-on-chronic liver failure (ACLF) after only once application of camrelizumab; the patient underwent serological conversion of hepatitis B surface antigen (HBsAg) with liver injury. The patient's condition progressed rapidly. We added corticosteroids and applied plasma dialysis, along with tenofovir alafenamide (TAF) to control HBV. However, the patient eventually died of liver failure. To our knowledge, there are few reports of HBsAg clearance due to ICIs accompanied by fatal acute-on-chronic liver failure shortly after ICIs initiation. These results suggest that ICIs can cause fatal liver injury in a short term; in patients with chronic HBV infection, ICIs use may promote serological conversion of HBsAg.
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Affiliation(s)
| | | | | | - Jing Liang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extra-corporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin, China
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Guo Y, Zeng X, Li L, Wang L. The impact of HBV infection on clinical outcomes of COVID-19 patients: a systematic review and meta-analysis. Epidemiol Infect 2023; 151:e135. [PMID: 37381822 PMCID: PMC10540167 DOI: 10.1017/s0950268823000705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/30/2023] Open
Abstract
The impact of hepatitis B virus (HBV) infection on clinical outcomes of coronavirus disease 2019 (COVID-19) remains unclear. The aim of this study is to explore this impact. For this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, Cochrane library, China National Knowledge Infrastructure (CKNI), China Science and Technology Journal Database (VIP), and Wan Fang database for articles between 1 January 2020 and 1 February 2023. We used the Newcastle-Ottawa Quality Assessment to evaluate the study's quality. A random-effects meta-analysis was performed utilising the rates of severe/critical illness and death in COVID-19 patients with and without HBV infection. Eighteen studies with a total of 40,502 participants met the inclusion criteria. The meta-analysis showed that compared to those without HBV infection, COVID-19 patients with HBV were at increased risk of mortality (OR = 1.65, I2 = 58%, and 95% CI 1.08-2.53) and severity (OR = 1.90, I2 = 44%, and 95% CI 1.62-2.24). The region and gender may influence the outcomes of COVID-19 patients with HBV infection, but it requires more global data to confirm. In conclusion, HBV infection is significantly linked to an increased risk of severity and mortality in COVID-19.
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Affiliation(s)
- Yifan Guo
- Emergency Department of Infectious Diseases of Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xueling Zeng
- Emergency Department of Infectious Diseases of Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Li Li
- Emergency Department of Infectious Diseases of Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Linghang Wang
- Emergency Department of Infectious Diseases of Beijing Ditan Hospital, Capital Medical University, Beijing, China
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Luo J, Zheng Z, Yu R. Analysis of medical malpractice liability disputes related to novel antineoplastic drugs and research on risk prevention and control strategies. PLoS One 2023; 18:e0286623. [PMID: 37276214 DOI: 10.1371/journal.pone.0286623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 05/22/2023] [Indexed: 06/07/2023] Open
Abstract
OBJECTIVE To investigate the general characteristics of litigation cases of medical malpractice liability disputes (MMLDs) related to novel antineoplastic drugs (NADs), the drugs involved, as well as the common types of medical errors related to NADs and their damages in the process of diagnosis and treatment, with the aims of improving the level of rational medication use in the clinical application of NADs and actively prevent medical disputes. METHODS The China Judgments Online was searched for the cause of action using the key word "MMLDs" along with the name of 77 kinds of NADs. A total of 39 NAD litigation cases meeting the inclusion criteria from 1 January 2009 to 31 December 2021 were analyzed, and each potential adverse drug reaction (ADR) was reviewed to determine a causality assessment using the Naranjo algorithm for non-drug-induced liver injury (DILI) cases and the updated Roussel Uclaf Causality Assessment Method (RUCAM) for the DILI cases. Risk prevention and control strategies were recommended. RESULTS Cases that met the inclusion criteria increased substantially each year during the last six years, from three cases in 2009-2015 to 36 cases in 2016-2021. There were more cases in Eastern China than in other geographic regions. Most cases involved tertiary hospitals, patients between 25 and 60 years of age, and patients who were predominately male. There were 18 kinds of NADs involved in medical errors. The most common consequences of NADs were closely related to the death, disability, and increased treatment costs caused by ADRs, inadequate indications, delayed diagnosis and treatment, and misdiagnosis and mistreatment. The most frequent medical errors were medical technology errors, medical ethics errors and medical record writing/safekeeping errors. In two cases involving DILI, one case was unable to undergo further RUCAM scoring because the liver function indicators of the patient before and after treatment were not published. CONCLUSION The establishment of mechanisms to reduce the risks associated with the clinical application of NADs is warranted. Healthcare services must maintain strict adherence to the specific requirements of GPCANADs and drug instructions and strictly grasp the indications, contraindications, usage, and dosage of drugs, and strengthen the notification and management of off-label drug use. Monitoring patients for ADRs and preparing rescue and treatment measures for high-risk drugs may serve to reduce damages related to NADs. For DILI cases, medical and appraisal institutions should use RUCAM score to assess causal relationships.
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Affiliation(s)
- Jinyu Luo
- Division of Nursing, Hemopurification Center, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang Province, People's Republic of China
| | - Zaoqian Zheng
- Department of Pharmacy, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, People's Republic of China
- Division of Medical Administration, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, People's Republic of China
- Division of Medical Administration, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, People's Republic of China
| | - Rongliang Yu
- Division of Medical Administration, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, People's Republic of China
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Bahrulolum H, Tarrahimofrad H, Rouzbahani FN, Nooraei S, Sameh MM, Hajizade A, Ahmadian G. Potential of CRISPR/Cas system as emerging tools in the detection of viral hepatitis infection. Virol J 2023; 20:91. [PMID: 37158910 PMCID: PMC10165583 DOI: 10.1186/s12985-023-02048-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 04/23/2023] [Indexed: 05/10/2023] Open
Abstract
Viral hepatitis, the most common cause of inflammatory liver disease, affects hundreds of millions of people worldwide. It is most commonly associated with one of the five nominal hepatitis viruses (hepatitis A-E viruses). HBV and HCV can cause acute infections and lifelong, persistent chronic infections, while HAV and HEV cause self-limiting acute infections. HAV and HEV are predominantly transmitted through the fecal-oral route, while diseases transmitted by the other forms are blood-borne diseases. Despite the success in the treatment of viral hepatitis and the development of HAV and HBV vaccines, there is still no accurate diagnosis at the genetic level for these diseases. Timely diagnosis of viral hepatitis is a prerequisite for efficient therapeutic intervention. Due to the specificity and sensitivity of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated sequences (Cas) technology, it has the potential to meet critical needs in the field of diagnosis of viral diseases and can be used in versatile point-of-care (POC) diagnostic applications to detect viruses with both DNA and RNA genomes. In this review, we discuss recent advances in CRISPR-Cas diagnostics tools and assess their potential and prospects in rapid and effective strategies for the diagnosis and control of viral hepatitis infection.
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Affiliation(s)
- Howra Bahrulolum
- Department of Industrial and Environmental and Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, 1497716316 Iran
| | - Hossein Tarrahimofrad
- Department of Animal Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, 1497716316 Iran
| | - Fatemeh Nouri Rouzbahani
- Department of Industrial and Environmental and Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, 1497716316 Iran
| | - Saghi Nooraei
- Department of Industrial and Environmental and Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, 1497716316 Iran
| | - Mehdi Mousavi Sameh
- Department of Industrial and Environmental and Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, 1497716316 Iran
| | - Abbas Hajizade
- Applied Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, 1435916471 Iran
| | - Gholamreza Ahmadian
- Department of Industrial and Environmental and Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, 1497716316 Iran
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Khanam A, Ghosh A, Chua JV, Kottilil S. Blockade of CCR4 breaks immune tolerance in chronic hepatitis B patients by modulating regulatory pathways. J Transl Med 2023; 21:271. [PMID: 37081509 PMCID: PMC10120209 DOI: 10.1186/s12967-023-04104-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 04/04/2023] [Indexed: 04/22/2023] Open
Abstract
BACKGROUND Immunotargets including checkpoint inhibitors and toll-like receptor 8 agonists have recently gained attention for the recovery of hepatitis B virus (HBV)-specific T cell exhaustion in chronic hepatitis B(CHB). Chemokine receptors have a similar significant role during viral infections; however, their role in CHB remains poorly understood. Therefore, in this study we evaluated the role of chemokine receptor 4 (CCR4) in deriving immunosuppression during CHB. METHODS We characterized CCR4+CD8+ T cells in CHB and identified their involvement in immunosuppression. Further, we examined if CCR4 blockade with mogamulizumab antibody can recover the functional exhaustion in HBsAg-specific T cells. RESULTS CHB patients exhibit higher frequency of CCR4+CD8+ T cells that increase with higher HBsAg levels and fibrosis scores. In vitro, HBs antigen triggers CCR4 expression. These cells express multiple inhibitory receptors and exhibit immunosuppressive functions by producing excessive immunoregulatory cytokines IL-4, IL-5, IL-10 and TGF-β1. CCR4 Blockade significantly boosted HBsAg-specific antiviral-cytokine production(IFN-γ, TNF-α and IL-21) in T cells through enhancing their proliferation capacity and polarizing these cells towards T helper 1(Th1) and T follicular helper cells(TFH) in case of CD4 cells, and cytotoxic T cell 1(TC1) and cytotoxic T follicular(TCF) cells in case of CD8. Cytotoxic potential was improved, while no induction of immunosuppressive-cytokines was seen after anti-CCR4 treatment thereby eliminating the risk of treatment-induced immunosuppression. CCR4 blockade inhibited the development and effector function of Tregs by controlling their expansion and TGF-β1 production preventing Tregs-induced immunotolearance. CONCLUSIONS CCR4 blockade reconstitutes antiviral immune response in T cells and limits the immunosuppressive functions of Tregs, representing them as a promising immunotherapeutic target for functional cure of CHB.
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Affiliation(s)
- Arshi Khanam
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
| | - Alip Ghosh
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Joel V Chua
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Shyam Kottilil
- Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
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Relevance of HBx for Hepatitis B Virus-Associated Pathogenesis. Int J Mol Sci 2023; 24:ijms24054964. [PMID: 36902395 PMCID: PMC10003785 DOI: 10.3390/ijms24054964] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/20/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023] Open
Abstract
The hepatitis B virus (HBV) counts as a major global health problem, as it presents a significant causative factor for liver-related morbidity and mortality. The development of hepatocellular carcinomas (HCC) as a characteristic of a persistent, chronic infection could be caused, among others, by the pleiotropic function of the viral regulatory protein HBx. The latter is known to modulate an onset of cellular and viral signaling processes with emerging influence in liver pathogenesis. However, the flexible and multifunctional nature of HBx impedes the fundamental understanding of related mechanisms and the development of associated diseases, and has even led to partial controversial results in the past. Based on the cellular distribution of HBx-nuclear-, cytoplasmic- or mitochondria-associated-this review encompasses the current knowledge and previous investigations of HBx in context of cellular signaling pathways and HBV-associated pathogenesis. In addition, particular focus is set on the clinical relevance and potential novel therapeutic applications in the context of HBx.
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Etienne S, Vosbeck J, Bernsmeier C, Osthoff M. Prevention of Hepatitis B Reactivation in Patients Receiving Immunosuppressive Therapy: a Case Series and Appraisal of Society Guidelines. J Gen Intern Med 2023; 38:490-501. [PMID: 36138278 PMCID: PMC9905451 DOI: 10.1007/s11606-022-07806-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 09/08/2022] [Indexed: 12/03/2022]
Abstract
Hepatitis B (HBV) reactivation (HBVr) is a potentially fatal complication in patients with past HBV exposure receiving immunosuppressive therapy. HBVr can occur in patients with chronic HBV infection as well as in patients with resolved HBV infection. In this article, we present the cases of four patients with resolved hepatitis B who presented with HBVr during or after immunosuppressive treatment, of whom two died as a consequence of HBVr. We then reflect on and summarize the recommendations of four major societies for the screening and management of previously HBV-exposed patients planned to receive immunosuppressive treatment. Current guidelines recommend screening for HBV in all patients planned to receive immunosuppressive therapy. Risk of HBVr is assessed based on the serological status of the patient and the planned immunosuppressive drug regimen. For patients considered to be at low risk of HBVr, management consists of serological monitoring for HBVr and immediate preemptive antiviral therapy in the case of HBVr. For patients considered to be at intermediate or high risk for HBVr, antiviral prophylaxis should be initiated concordantly with the immunosuppressive therapy and continued for up to 18 months after cessation of the immunosuppressive regimen. Areas of uncertainty include the risk of novel and emerging immunosuppressive and immune modulatory drugs and the exact duration of antiviral prophylaxis. Greater awareness is needed among clinicians regarding the risk of HBVr in patients receiving immunosuppressive therapy, especially in low-endemicity settings. Implementation of screening and management programs and decision support tools based on the presented guidelines may improve the management of these patients.
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Affiliation(s)
- Samuel Etienne
- Division of Internal Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland
| | - Jürg Vosbeck
- Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
| | | | - Michael Osthoff
- Division of Internal Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland.
- Department of Clinical Research, University of Basel, Basel, Switzerland.
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Ward JW, Wanlapakorn N, Poovorawan Y, Shouval D. Hepatitis B Vaccines. PLOTKIN'S VACCINES 2023:389-432.e21. [DOI: 10.1016/b978-0-323-79058-1.00027-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Chen YF, Wang Y, Wang Y, Luo YL, Lu ZD, Du XJ, Xu CF, Wang J. Optimized Cationic Lipid-assisted Nanoparticle for Delivering CpG Oligodeoxynucleotides to Treat Hepatitis B Virus Infection. Pharm Res 2023; 40:145-156. [PMID: 36002611 DOI: 10.1007/s11095-022-03307-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Accepted: 05/25/2022] [Indexed: 11/29/2022]
Abstract
PURPOSE Hepatitis B virus (HBV) infection is such a global health problem that hundreds of millions of people are HBV carriers. Current anti-viral agents can inhibit HBV replication, but can hardly eradicate HBV. Cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) are an adjuvant that can activate plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs) to induce therapeutic immunity for HBV eradication. However, efficient delivery of CpG ODNs into pDCs and cDCs remains a challenge. In this study, we constructed a series of cationic lipid-assisted nanoparticles (CLANs) using different cationic lipids to screen an optimal nanoparticle for delivering CpG ODNs into pDCs and cDCs. METHODS We constructed different CLANCpG using six cationic lipids and analyzed the cellular uptake of different CLANCpG by pDCs and cDCs in vitro and in vivo, and further analyzed the efficiency of different CLANCpG for activating pDCs and cDCs in both wild type mice and HBV-carrier mice. RESULTS We found that CLAN fabricated with 1,2-Dioleoyl-3-trimethylammonium propane (DOTAP) showed the highest efficiency for delivering CpG ODNs into pDCs and cDCs, resulting in strong therapeutic immunity in HBV-carrier mice. By using CLANCpG as an immune adjuvant in combination with the injection of recombinant hepatitis B surface antigen (rHBsAg), HBV was successfully eradicated and the chronic liver inflammation in HBV-carrier mice was reduced. CONCLUSION We screened an optimized CLAN fabricated with DOTAP for efficient delivery of CpG ODNs to pDCs and cDCs, which can act as a therapeutic vaccine adjuvant for treating HBV infection.
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Affiliation(s)
- Yi-Fang Chen
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 511442, People's Republic of China
| | - Yan Wang
- School of Medicine, South China University of Technology, Guangzhou, 510006, People's Republic of China
| | - Yue Wang
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 511442, People's Republic of China.,National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, People's Republic of China.,Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, 510006, People's Republic of China
| | - Ying-Li Luo
- School of Medicine, South China University of Technology, Guangzhou, 510006, People's Republic of China
| | - Zi-Dong Lu
- School of Medicine, South China University of Technology, Guangzhou, 510006, People's Republic of China
| | - Xiao-Jiao Du
- School of Medicine, South China University of Technology, Guangzhou, 510006, People's Republic of China.
| | - Cong-Fei Xu
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 511442, People's Republic of China. .,National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, People's Republic of China.
| | - Jun Wang
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 511442, People's Republic of China.,National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, People's Republic of China.,Guangdong Provincial Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou, 510006, People's Republic of China
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Tagliamento M, Remon J, Giaj Levra M, De Maria A, Bironzo P, Besse B, Novello S, Mezquita L. Immune Checkpoint Inhibitors in Patients With Cancer and Infection by Hepatitis B or C Virus: A Perspective Through the Results of a European Survey. JTO Clin Res Rep 2022; 4:100446. [PMID: 36687558 PMCID: PMC9853354 DOI: 10.1016/j.jtocrr.2022.100446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 11/09/2022] [Accepted: 12/02/2022] [Indexed: 12/16/2022] Open
Abstract
Introduction Patients with cancer and hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are underrepresented in several clinical trials testing immune checkpoint inhibitors (ICIs). Consequently, safety and efficacy of ICI therapy in this population have not been completely defined. We aimed to evaluate the attitudes of oncologists on this topic. Methods We conducted a 14-item European anonymous online survey. Results Physicians from 56 oncology departments (26 from Italy, 15 from France, and 15 from Spain) took part in the survey. They mainly used to prescribe ICIs for treating patients with lung cancer, melanoma, and renal cell carcinoma. Of them, 95% recognized the need for specific guidelines addressing the management of patients with cancer and HBV or HCV treated with ICIs. Just 63% of the respondents screened patients for HBV and HCV status before ICIs initiation, although the risk of immune-related hepatotoxicity or viral reactivation was a major concern for most of them. Only 9% of the surveyed oncologists considered HBV and HCV infection a major exclusion criterion for receiving ICIs. Furthermore, 29% of the respondents would start a prophylactic treatment of active infection at ICIs initiation. Conclusions ICIs administration in patients with cancer and HBV or HCV infection is of concern for most of the surveyed European oncologists. Nonetheless, active screening and treatment of viral hepatitis should be improved. Data in this specific setting are needed for an evidence-based management and should be generated by broadening inclusion criteria of clinical trials to allow the enrollment of patients with HBV and HCV.
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Affiliation(s)
- Marco Tagliamento
- Cancer Medicine Department, Gustave Roussy, Villejuif, France,Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genova, Genova, Italy,Corresponding author. Address for correspondence: Marco Tagliamento, MD, Cancer Medicine Department, Gustave Roussy, 114 Rue Edouard Vaillant, 94805 Villejuif, France.
| | - Jordi Remon
- Department of Medical Oncology, Centro Integral Oncológico Clara Campal (HM-CIOCC), Hospital HM Delfos, Barcelona, Spain
| | | | - Andrea De Maria
- Division of Infectious Diseases, IRCCS Ospedale Policlinico San Martino, DISSAL, University of Genova, Genova, Italy
| | - Paolo Bironzo
- Thoracic Oncology Unit, Department of Oncology, San Luigi Hospital, University of Torino, Orbassano, Italy
| | - Benjamin Besse
- Cancer Medicine Department, Gustave Roussy, Villejuif, France
| | - Silvia Novello
- Thoracic Oncology Unit, Department of Oncology, San Luigi Hospital, University of Torino, Orbassano, Italy
| | - Laura Mezquita
- Division of Medical Oncology, Hospital Clínic, Barcelona, Spain,Laboratory of Translational Genomic and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain
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Wang L, Zhang G, Sun Y, Wu Z, Ren C, Zhang Z, Peng X, Zhang Y, Zhao Y, Li C, Gao L, Liang X, Sun H, Cui J, Ma C. Enhanced Delivery of TLR7/8 Agonists by Metal-Organic Frameworks for Hepatitis B Virus Cure. ACS APPLIED MATERIALS & INTERFACES 2022; 14:46176-46187. [PMID: 36206454 DOI: 10.1021/acsami.2c11203] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Hepatitis B virus (HBV) infection remains a major challenge to global health due to unsatisfactory treatment efficacy, side effects of current therapies, and immune tolerance. Toll-like receptors 7/8 (TLR7/8) agonists have shown great potential in chronic hepatitis B (CHB) cure, but systemic administration often induces severe side effects due to rapid dispersion into the microvasculature. Herein, we encapsulate an imidazoquinoline-based TLR7/8 agonist (IMDQ) into zeolitic imidazolate framework 8 nanoparticles (IMDQ@ZIF-8 NPs) for HBV immunotherapy. Compared with free IMDQ, IMDQ@ZIF-8 NPs efficiently accumulate in the liver and are selectively taken up by antigen-presenting cells (APCs), leading to enhanced APC activation and efficient viral elimination in HBV-infected models. Strikingly, MDQ@ZIF-8 NP treatment results in the obvious production of anti-HBs antibody and seroconversion in HBV-infected mice. Overall, this study on the convergence of a facile assembly approach and efficient therapeutic effects represents a promising strategy for HBV treatment.
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Affiliation(s)
- Liyuan Wang
- Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong University, Jinan, Shandong 250012, China
- Department of Microbiology, Weifang Medical University, Weifang, Shandong 261042, China
| | - Guiqiang Zhang
- Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China
- Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Science, Jinan, Shandong 250117, China
| | - Yang Sun
- Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong University, Jinan, Shandong 250012, China
| | - Zhuanchang Wu
- Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong University, Jinan, Shandong 250012, China
| | - Caiyue Ren
- Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong University, Jinan, Shandong 250012, China
| | - Zhaoying Zhang
- Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong University, Jinan, Shandong 250012, China
| | - Xueqi Peng
- Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong University, Jinan, Shandong 250012, China
| | - Yankun Zhang
- Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong University, Jinan, Shandong 250012, China
| | - Ying Zhao
- Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong University, Jinan, Shandong 250012, China
| | - Chunyang Li
- Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Infection and Immunity of Shandong Province, Shandong University, Jinan, Shandong 250012, China
| | - Lifen Gao
- Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Infection and Immunity of Shandong Province, Shandong University, Jinan, Shandong 250012, China
| | - Xiaohong Liang
- Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Infection and Immunity of Shandong Province, Shandong University, Jinan, Shandong 250012, China
| | - Haifeng Sun
- Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China
| | - Jiwei Cui
- Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China
| | - Chunhong Ma
- Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong University, Jinan, Shandong 250012, China
- Key Laboratory of Infection and Immunity of Shandong Province, Shandong University, Jinan, Shandong 250012, China
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Spera AM. Hepatitis B virus infection reactivation in patients under immunosuppressive therapies: Pathogenesis, screening, prevention and treatment. World J Virol 2022; 11:275-282. [PMID: 36188738 PMCID: PMC9523324 DOI: 10.5501/wjv.v11.i5.275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 05/20/2022] [Accepted: 07/26/2022] [Indexed: 02/05/2023] Open
Abstract
With a 5.3% of the global population involved, hepatitis B virus (HBV) is a major public health challenge requiring an urgent response. After a possible acute phase, the natural history of HBV infection can progress in chronicity. Patients with overt or occult HBV infection can undergo HBV reactivation (HBVr) in course of immunosuppressive treatments that, apart from oncological and hem-atological diseases, are also used in rheumatologic, gastrointestinal, neurological and dermatological settings, as well as to treat severe acute respiratory syndrome coronavirus 2 infection. The risk of HBV reactivation is related to the immune status of the patient and the baseline HBV infection condition. The aim of the present paper is to investigate the risk of HBVr in those not oncological settings in order to suggest strategies for preventing and treating this occurrence. The main studies about HBVr for patients with occult hepatitis B infection and chronic HBV infection affected by non-oncologic diseases eligible for immunosuppressive treatment have been analyzed. The occurrence of this challenging event can be reduced screening the population eligible for immunosuppressant to assess the best strategies according to any virological status. Further prospective studies are needed to increase data on the risk of HBVr related to newer immunomodulant agents employed in non-oncological setting.
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Affiliation(s)
- Anna Maria Spera
- Infectious Disease Unit, Universitary Hospital OORR San Giovanni di Dio e Ruggi d'Aragona, Salerno 84131, Italy
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Hepatitis B virus reactivation in patients undergoing immune checkpoint inhibition: systematic review with meta-analysis. J Cancer Res Clin Oncol 2022; 149:1993-2008. [PMID: 35767193 DOI: 10.1007/s00432-022-04133-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 06/10/2022] [Indexed: 10/17/2022]
Abstract
PURPOSE Immune checkpoint inhibitors (ICIs) have been explored as first-line treatment in various types of previously untreatable malignancies, while limited evidence is available on the management of hepatitis B virus (HBV) in patients undergoing immunotherapy. We systematically reviewed data concerning challenges of hepatic adverse events including HBV reactivation and hepatitis in patients with chronic HBV infection undergoing immunotherapy. METHODS A systematic search was conducted in Medline, web of science, Embase and Cochrane library up to May 31, 2022. Studies reporting the safety profile of ICIs in patients with HBV infection were eligible. Meta-analyses were conducted to generate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS A total of 13 studies including 2561 patients were included for meta-analysis. The overall incidence rates of HBV reactivation in patients with chronic HBV infection and past HBV infection were 1.0% (95% CI 0-3%) and 0% (95% CI 0-0%), respectively. Among patients with chronic HBV infection, the incidence rates of HBV reactivation were 1.0% (95% CI 0-2%) and 10.0% (95% CI 4-18%) for patients with and without antiviral prophylaxis, respectively. Patients with chronic HBV infection were at a higher risk of HBV reactivation compared with those with past HBV infection [OR = 8.69, 95% CI (2.16-34.99)]. Antiviral prophylaxis significantly reduced the risk of HBV reactivation [OR = 0.12, 95% CI (0.02-0.67)] and HBV-associated hepatitis [OR = 0.05, 95% CI (0.01-0.28)] in patients with chronic HBV infection. CONCLUSIONS Prophylactic antiviral therapy should be administered to patients with chronic HBV infection undergoing anticancer immunotherapy. Patients with past HBV infection are at lower risk of HBV reactivation compared with those with chronic HBV infection, they could be initiated with antiviral prophylaxis or monitored with the intent of on-demand antiviral therapy.
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Han K, He T, Huang S, Sun W, Gao Y. Blood Lead Exposure and Association With Hepatitis B Core Antibody in the United States: NHANES 2011–2018. Front Public Health 2022; 10:873741. [PMID: 35774563 PMCID: PMC9239404 DOI: 10.3389/fpubh.2022.873741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 05/04/2022] [Indexed: 11/24/2022] Open
Abstract
The objective of this project was to explore the distribution and related factors of blood lead and the association between blood lead and hepatitis B core antibody (HBcAb). All the data were from the U.S. National Health and Nutrition Examination Survey (NHANES). In total, 15,097 (aged 20–80 years) participants were included. Participants without a history of blood transfusion were more likely to be exposed to lower levels of blood lead [−2.30 (−3.13, −1.47) for HBcAb (–) and −2.23 (−4.54, 0.08) for HBcAb (+)]. The odds ratio (OR) of HBcAb (+) increased with blood lead and the result was 1.09 (1.06, 1.12). This study showed that older adults, men, people with a lower education level, a lower ratio of family income to poverty (PIR), a lower body mass index (BMI), or a history of blood transfusion, people who lived with a companion or with a total number of people in the family >3, people living in the United States for a longer time, U.S. citizens by birth or naturalization, and people not born in the United States were associated with higher blood lead exposure, and blood lead had a positive association with HBcAb (+).
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Research Progress on the Mechanism of Persistent Low-Level HBsAg Expression in the Serum of Patients with Chronic HBV Infection. J Immunol Res 2022; 2022:1372705. [PMID: 35465353 PMCID: PMC9020929 DOI: 10.1155/2022/1372705] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 03/28/2022] [Indexed: 12/17/2022] Open
Abstract
Among HBV-infected persons, there is a group of people with hepatitis B surface antigen (HBsAg) showing persistently low levels of expression. The production of low-level HBsAg does not mean a good outcome of chronic HBV infection. Patients still have virus replication and sustained liver damage, and they have the potential to transmit the infection. This risk poses a challenge to clinical diagnosis and blood transfusion safety and is a major concern of experts. However, the mechanism behind persistent low-level HBsAg expression in serum is not completely clear, and complete virus clearance by the host is vital. In this review, we summarize the research progress on the mechanism behind low-level expression of HBsAg in patients with chronic HBV infection in recent years.
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Krajnc N, Bsteh G, Berger T, Mares J, Hartung HP. Monoclonal Antibodies in the Treatment of Relapsing Multiple Sclerosis: an Overview with Emphasis on Pregnancy, Vaccination, and Risk Management. Neurotherapeutics 2022; 19:753-773. [PMID: 35378683 PMCID: PMC8978776 DOI: 10.1007/s13311-022-01224-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/14/2022] [Indexed: 01/10/2023] Open
Abstract
Monoclonal antibodies have become a mainstay in the treatment of patients with relapsing multiple sclerosis (RMS) and provide some benefit to patients with primary progressive MS. They are highly precise by specifically targeting molecules displayed on cells involved in distinct immune mechanisms of MS pathophysiology. They not only differ in the target antigen they recognize but also by the mode of action that generates their therapeutic effect. Natalizumab, an [Formula: see text]4[Formula: see text]1 integrin antagonist, works via binding to cell surface receptors, blocking the interaction with their ligands and, in that way, preventing the migration of leukocytes across the blood-brain barrier. On the other hand, the anti-CD52 monoclonal antibody alemtuzumab and the anti-CD20 monoclonal antibodies rituximab, ocrelizumab, ofatumumab, and ublituximab work via eliminating selected pathogenic cell populations. However, potential adverse effects may be serious and can necessitate treatment discontinuation. Most importantly, those are the risk for (opportunistic) infections, but also secondary autoimmune diseases or malignancies. Monoclonal antibodies also carry the risk of infusion/injection-related reactions, primarily in early phases of treatment. By careful patient selection and monitoring during therapy, the occurrence of these potentially serious adverse effects can be minimized. Monoclonal antibodies are characterized by a relatively long pharmacologic half-life and pharmacodynamic effects, which provides advantages such as permitting infrequent dosing, but also creates disadvantages regarding vaccination and family planning. This review presents an overview of currently available monoclonal antibodies for the treatment of RMS, including their mechanism of action, efficacy and safety profile. Furthermore, we provide practical recommendations for risk management, vaccination, and family planning.
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Affiliation(s)
- Nik Krajnc
- Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Gabriel Bsteh
- Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Thomas Berger
- Department of Neurology, Medical University of Vienna, Vienna, Austria
| | - Jan Mares
- Department of Neurology, Palacky University Olomouc, Olomouc, Czech Republic
| | - Hans-Peter Hartung
- Department of Neurology, Medical University of Vienna, Vienna, Austria.
- Department of Neurology, Palacky University Olomouc, Olomouc, Czech Republic.
- Department of Neurology, Medical Faculty, Heinrich-Heine University, Moorenstrasse 5, 40225, Düsseldorf, Germany.
- Brain and Mind Center, University of Sydney, Sydney, Australia.
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Librero Jiménez M, López Garrido MÁ, Fernández Cano MC. Letter to the editor: Reactivation of HBV triggered by SARS-CoV-2 in a patient with cirrhosis. Hepatology 2022; 75:765-766. [PMID: 34888903 PMCID: PMC9015477 DOI: 10.1002/hep.32271] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 12/08/2022]
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Khan MM, Ali MJ, Hanif H, Maqsood MH, Ahmad I, Alvarez JEG, Catana MA, Lau DTY. OUP accepted manuscript. Gastroenterol Rep (Oxf) 2022; 10:goac018. [PMID: 35663152 PMCID: PMC9154071 DOI: 10.1093/gastro/goac018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 03/04/2022] [Accepted: 04/24/2022] [Indexed: 11/25/2022] Open
Abstract
Hepatitis B virus (HBV) remains a global public health problem despite the availability of effective vaccine and antiviral therapy. Cytomegalovirus (CMV), another hepatotropic virus, is also very prevalent in the general population worldwide. Both HBV and CMV can persist in the host and have potential to reactivate especially with weakened host cellular immunity. Superimposed CMV infection can lead to severe HBV reactivation. The pathogenesis of the co-infection of HBV and CMV remains poorly understood. Studies reported conflicting results regarding the inhibitory effect of CMV on HBV replication. There is an unmet need on the management of co-infection of HBV and CMV; research initiatives dedicated to understanding their interactions are urgently needed.
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Affiliation(s)
- Muzammil M Khan
- Department of Medicine, Division of Gastroenterology, Liver Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Mukarram J Ali
- Department of Medicine, Division of Gastroenterology, Liver Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Hira Hanif
- Department of Medicine, Division of Gastroenterology, Liver Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Muhammad H Maqsood
- Department of Medicine, Division of Gastroenterology, Liver Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Imama Ahmad
- Department of Medicine, North Shore Medical Center, Salem, MA, USA
| | - Javier E G Alvarez
- Department of Medicine, Division of Gastroenterology, Liver Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Maria-Andreea Catana
- Department of Medicine, Division of Gastroenterology, Liver Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Daryl T Y Lau
- Department of Medicine, Division of Gastroenterology, Liver Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- Corresponding author. Department of Medicine, Liver Research Center, 110 Francis Street, Suite 4A, Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Tel: +1 (617) 632-1070; Fax: (617) 632-1065;
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Onorato L, Pisaturo M, Camaioni C, Grimaldi P, Codella AV, Calò F, Coppola N. Risk and Prevention of Hepatitis B Virus Reactivation during Immunosuppression for Non-Oncological Diseases. J Clin Med 2021; 10:5201. [PMID: 34768721 PMCID: PMC8584565 DOI: 10.3390/jcm10215201] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 10/30/2021] [Accepted: 11/03/2021] [Indexed: 12/31/2022] Open
Abstract
Reactivation of overt or occult HBV infection (HBVr) is a well-known, potentially life-threatening event which can occur during the course of immunosuppressive treatments. Although it has been described mainly in subjects receiving therapy for oncological or hematological diseases, the increasing use of immunosuppressant agents in non-oncological patients observed in recent years has raised concerns about the risk of reactivation in several other settings. However, few data can be found in the literature on the occurrence of HBVr in these populations, and few clear recommendations on its management have been defined. The present paper was written to provide an overview of the risk of HBV reactivation in non-neoplastic patients treated with immunosuppressive drugs, particularly for rheumatological, gastrointestinal, dermatological and neurological diseases, and for COVID-19 patients receiving immunomodulating agents; and to discuss the potential strategies for prevention and treatment of HBVr in these settings.
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Affiliation(s)
- Lorenzo Onorato
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
| | - Mariantonietta Pisaturo
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
| | - Clarissa Camaioni
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
| | - Pierantonio Grimaldi
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
| | - Alessio Vinicio Codella
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
| | - Federica Calò
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
| | - Nicola Coppola
- Department of Mental Health and Public Medicine, Faculty of Medicine, University of Campania Luigi Vanvitelli, Via L. Armanni 5, 80138 Naples, Italy; (L.O.); (M.P.); (C.C.); (P.G.)
- Infectious Diseases Unit, Azienda Ospedaliera Universitaria Luigi Vanvitelli, Via Pansini 5, 80138 Naples, Italy; (A.V.C.); (F.C.)
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Shaikh SA, Kahn J, Aksentijevic A, Kawewat-Ho P, Bixby A, Rendulic T, Park JM. A multi-center evaluation of hepatitis B reactivation with and without antiviral prophylaxis after kidney transplantation. Transpl Infect Dis 2021; 24:e13751. [PMID: 34725887 DOI: 10.1111/tid.13751] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 10/10/2021] [Accepted: 10/22/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) positive kidney transplant recipients ranges between 1.4-9.6%. Limited evidence is available regarding routine antiviral prophylaxis and identifiable risk factors for HBV reactivation in this population. METHODS In this multi-center retrospective study, we evaluated the prevalence of HBV reactivation in HBsAg-negative anti-HBc-positive kidney transplant recipients who did or did not receive antiviral prophylaxis. The primary outcome assessed the prevalence of HBV reactivation, defined as a positive HBV DNA by PCR of any viral load at or above the minimal detection level. The principal safety outcomes assessed 1-year graft survival, 1-year all-cause mortality, biopsy proven acute rejection (BPAR), and antibody mediated rejection (AMR). RESULTS One-hundred sixty-one patients met inclusion criteria and comprised of two groups, antiviral prophylaxis (n=14) and no antiviral prophylaxis (n=147). Of patients who did not receive prophylaxis only five (3.4%) experienced HBV reactivation whereas one (7.1%) patient in the prophylaxis group experienced reactivation over a median follow-up of 1103 days (p= 0.43). Furthermore, there were no differences with respect to all secondary outcomes. Statistical analysis demonstrated delayed graft function to be a significant factor associated with HBV reactivation. CONCLUSION These study results suggest that the prevalence of HBV reactivation in HBsAg-negative anti-HBc-positive kidney transplant recipients is low, regardless of antiviral prophylaxis. Furthermore, there were no significant graft related outcomes among those that did experience reactivation. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Suhail A Shaikh
- Keck Hospital of USC, Department of Transplant Surgery, University of Southern California, 1516 San Pablo St. #3269, Los Angeles, CA, 90033, USA
| | - Jeffrey Kahn
- Keck School of Medicine, Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, CA, USA
| | | | - Pnada Kawewat-Ho
- Keck Hospital of USC, Department of Transplant Surgery, University of Southern California, Los Angeles, CA, USA
| | - Alexandra Bixby
- University Hospitals Cleveland Medical Center, Department of Pharmacy Services, Cleveland, OH, USA
| | - TrisAnn Rendulic
- University of Kentucky HealthCare, Department of Pharmacy Services, Lexington, KY, USA
| | - Jeong M Park
- University of Michigan College of Pharmacy, Department of Clinical Pharmacy, Ann Arbor, MI, USA
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Khemichian S, Kahn J, Terrault NA. Use of Hepatitis B Virus-Positive Organs in Organ Transplantation. Clin Liver Dis 2021; 25:841-857. [PMID: 34593157 DOI: 10.1016/j.cld.2021.06.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The significant morbidity and mortality of people with end-stage renal, liver, heart, and lung diseases in need of transplantation provides rationale for use of organs from donors who are hepatitis B positive. The recipient's hepatitis B status plays a key role in defining the prophylactic strategy. The availability of safe and effective therapies (hepatitis B antivirals and hepatitis B immune globulin) has contributed to the safety of using hepatitis B-positive donors. The outcomes in both liver and nonliver solid organ transplant recipients given hepatitis B-positive organs have been excellent if appropriate prophylactic therapies provided.
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Affiliation(s)
- Saro Khemichian
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine at University of Southern California, 1520 San Pablo Street, Suite 1000, Los Angeles, CA 90033, USA
| | - Jeffrey Kahn
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine at University of Southern California, 1520 San Pablo Street, Suite 1000, Los Angeles, CA 90033, USA
| | - Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, Keck School of Medicine at University of Southern California, 1520 San Pablo Street, Suite 1000, Los Angeles, CA 90033, USA.
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Successful treatment by glecaprevir/pibrentasvir followed by hepatoprotective therapy of acute chronic hepatitis exacerbation caused by daratumumab-based regimen for multiple myeloma: Case report and review of the literature. J Infect Chemother 2021; 27:1750-1755. [PMID: 34344581 DOI: 10.1016/j.jiac.2021.07.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 07/06/2021] [Accepted: 07/26/2021] [Indexed: 01/06/2023]
Abstract
Hepatitis C virus (HCV) exacerbation is relatively rare as compared with hepatitis B virus reactivation in patients treated with immunosuppressive or anticancer drugs. We herein present the first reported case of acute exacerbation of chronic hepatitis in a patient with HCV persistent infection caused by combination treatment with daratumumab (DARA), bortezomib, and dexamethasone (DVd therapy). A 79-year-old woman diagnosed as having chronic HCV infection 11 years prior without successful viral elimination was referred to our hospital for the treatment of acute liver injury. Multiple myeloma (MM; IgG-κ type) was diagnosed two years before referral and subjected to several treatments. She had commenced DVd therapy four months prior to admission. Since her liver enzymes did not normalize with drug discontinuation and hepatoprotective therapy, we suspected HCV exacerbation and began direct-acting antiviral (DAA) treatment with glecaprevir/pibrentasvir (GLE/PIB). Soon afterwards, her liver enzymes normalized, and she achieved a sustained virological response after 8 weeks of treatment. Clinicians should bear in mind HCV exacerbation when encountering chronic HCV with acute liver injury under MM treatment including a DARA-based regimen. In such cases, DAA therapy is an option when other urgent treatments are needed.
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